Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 350, Issue 5, pp 441–453

Molecular pharmacology of somatostatin receptors

  • Daniel Hoyer
  • Hermann Lübbert
  • Christian Bruns
Invited Review


The neuropeptide somatostatin (SRIF) is widely expressed in the brain and in the periphery in two main forms, SRIF-14 and SRIF-28. Similarly, the presence of SRIF receptors throughout the whole body has been reported. SRIF produces a variety of effects including modulation of hormone release (e.g. GH, glucagon, insulin), of neurotransmitter release (e.g. acetylcholine, dopamine, 5-HT), and its own release is modulated by many neurotransmitters. SRIF affects cognitive and behavioural processes, the endocrine system, the gastrointestinal tract and the cardiovascular system and also has tumor growth inhibiting effects. Initially, two classes of SRIF receptors have been proposed on the basis of biochemical and functional studies. However, the recent cloning of five putative SRIF receptor subtypes which belong to the G-protein coupled receptor superfamily suggests that SRIF mediates its various effects via a whole family of receptors. Here we review, in this new context, the molecular pharmacology of the SRIF receptor subtypes present in the brain and in the periphery, and address the question of nomenclature of SRIF receptors.

Key words

Somatostatin SRIF Receptor subtypes Molecular cloning Second messengers Pathology Nomenclature 



c[Cys-Lys-Asn p-Cl-Phe-Phe-d-Trp-Lys-Thr-Phe Thr-Ser-Cys]


d-Nal-c[Cys Tyr-d-Trp-Lys Val-Cys]-Thr-NH2


d-Phe-c[Cys Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2






d-Nal-Ala-Tyr-d-Trp-Lys-Val-Ala Thr-NH2











CGP 23996
















SMS 201-995



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  1. Altemus M, Pigott T, L'Heureux F, Davis CL, Rubinow DR, Murphy DL, Gold PW (1993) CSF somatostatin in obsessive-compulsive disorder. Am J Psychiatry 150:460–464Google Scholar
  2. Araujo DM, Lapchak PA, Collier B, Quirion R (1990) Evidence that somatostatin enhances endogenous acetylcholine release in the rat hippocampus. J Neurochem 55:1546–1555Google Scholar
  3. Arneric SP, Reis DJ (1986) Somatostatin and cholecystokinin octapeptide differentially modulate the release of [3H] acetylcholine from caudate nucleus but not cerebral cortex: role of dopamine receptor activation. Brain Res 374:153–161Google Scholar
  4. Barber DL, Gregor M, Soll AH (1987) Somatostatin and muscarinic inhibition of canine enteric endocrine cells: cellular mechanisms. Am J Physiol 253:G684-G689Google Scholar
  5. Barber DL, McGuire ME, Ganz MB (1989) β-Adrenergic and somatostatin receptors regulate Na-H exchange independent of cAMP. J Biol Chem 264:21038–21042Google Scholar
  6. Bauer W, Briner U, Doepfner W, Haller R, Huguenin R, Marbach P, Petcher TJ, Pless J (1982) SMS 201–995: A very potent and selective octapeptide analogue of somatostatin with prolonged action. Life Sci 31:1133–1140Google Scholar
  7. Beal MF, Mazurek MF, Svendsen CN, Bird ED, Martin JB (1986) Widespread reduction of somatostatin-like immunoreactivity in the cerebral cortex in Alzheimer's disease. Ann Neurol 20:489–495Google Scholar
  8. Bell GI, Reisine T (1993) Molecular biology of somatostatin receptors. Trends Neurosci 16:34–38Google Scholar
  9. Bissette G, Meyers B (1992) Somatostatin in Alzheimer's disease and depression. Life Sci 51:1389–1410Google Scholar
  10. Bonanno G, Raiteri M, Emson PC (1988) In vitro release of somatostatin from cerebral cortical slices: characterization of electrically evoked release. Brain Res 447:92–97Google Scholar
  11. Brazeau P, Vale W, Burgus R, Ling N, Butcher M, Rivier J, Guillemin R (1973) Hypothalamic polypeptide that inhibits secretion on immunoreactive pituitary growth hormone. Science 179:77–79Google Scholar
  12. Bruno JF, Xu Y, Song J, Berelowitz M (1992) Molecular cloning and functional expression of a brain-specific somatostatin receptor. Proc Natl Acad Sci USA 89:11151–11155Google Scholar
  13. Bruno JF, Xu Y, Song J, Berelowitz M (1993) Tissue distribution of somatostatin receptor subtype messenger ribonucleic acid in the rat. Endocrinology 133:2561–267Google Scholar
  14. Bruns Ch, Dietl MM, Palacios JM, Pless J (1990) Identification and characterization of somatostatin receptors in neonatal rat long bones. Biochem J 265:39–44Google Scholar
  15. Buscail L, Esteve JP, Prats H, Bayard F, Bell GI, Vaysse N, Suzini C (1993) Human somatostatin receptor hSSTR2 may mediate the antiproliferative effect of octreotide. Gastroenterology 104:816Google Scholar
  16. Buscail L, Delesque N, Esteve JP, Saint Laurent N, Prats H, Clerc P, Robberecht P, Bell GI, Liebow C, Schally AW, Vaysse N, Suzini C (1994) Stimulatiom of tyrosine phosphatase and inhibition of cell proliferation by somatostatin analogues: mediation by human somatostatin receptor subtypes SSTR1 and SSTR2. Proc Natl Acad Sci USA 91:2315–2319Google Scholar
  17. Cai R-Z, Szoke B, Lu R, Fu D, Redding TW, Schally AV (1986) Synthesis and biological activity of highly potent octapeptide analogs of somatostatin. Proc Natl Acad Sci USA 83:1896–1900Google Scholar
  18. Chesselet MF, Reisine T (1983) Somatostatin regulates dopamine release in rat stratal slices and cat caudate nucleus. J Neurosci 3:232–236Google Scholar
  19. Chneiweiss H, Glowinski J, Premont J (1984) Vasoactive intestinal polypeptide receptors linked to an adenylate cyclase, and their relationship with biogenic amine- and somatostatin-sensitive adenylate cyclases on central neuronal and glial cells in primary cultures. J Neurochem 44:779–786Google Scholar
  20. Cohen ML, Rosing E, Wiley KS, Slater IH (1978) Somatostatin inhibits adrenergic and cholinergic neurotransmission in smooth muscle. Life Sci 23:1659–1664Google Scholar
  21. Corness JD, Demchyshyn LL, Seeman P, Van Tol HH, Srikant CB, Kent G, Patel YC, Niznik HB (1993) A human somatostatin receptor (SSTR3), located on chromosome 22, displays preferential affinity for somatostatin-14 like peptides. FEBS Lett 321:279–84Google Scholar
  22. Czernik AJ, Petrack B (1983) Somatostatin receptor binding in rat cerebral cortex. J Biol Chem 258:5525–5530Google Scholar
  23. Dawbarn D, Rossor MN, Mountjoy CQ, Roth M, Emson PC (1986) Decreased somatostatin immunoreactivity but not neuropeptide Y immunoreactivity in cerebral cortex in senile dementia of Alzheimer type. Neurosci Lett 70:154–159Google Scholar
  24. Demchyshyn L, Srikant CB, Sunahara RK, Kent G, Seeman P, VanTol HHM, Panetta R, Patel YC, Niznik HB (1993) Cloning and expression of a human somatostatin-14-selective receptor variant (somatostatin receptor 4) located on chromosome 20. Mol Pharmacol 43:894–901Google Scholar
  25. DeNoble V, Hepler D, Barto R (1989) Cysteamine-induced depletion of somatostatin produces differential cognitive deficits in rats. Brain Res 482:42–48Google Scholar
  26. De Weille JR, Schmid-Antomarchi H, Fosset M, Lazdunski M (1989) Regulation of ATP-sensitive K+ channels in insulinoma cells: activation by somatostatin and protein kinase C and the role of cAMP. Proc Natl Acad Sci USA 86:2971–2975Google Scholar
  27. Dimech J, Feniuk W, Humphrey PPA (1993) Antagonist effects of seglitide (MK 678) at somatostatin receptors in guinea-pig isolated right atria. Br J Pharmacol 109:898–899Google Scholar
  28. Dorflinger LJ, Schonbrunn A (1983) Somatostatin inhibits basal and vasoactive intestinal polypeptide stimulated hormone release by different mechanisms in GH pituitary cells. Endocrinology 113: 1551–1558Google Scholar
  29. Epelbaum J (1986) Somatostatin in the central nervous system: physiological and pathological modifications. Prog Neurobiol 27:63–100Google Scholar
  30. Epelbaum J, Bertherat, J (1993) Localization and quantification of somatostatin receptors by light microscopic autoradiography. Methods Neurosci 12:279–292Google Scholar
  31. Epelbaum J, Dussaillant M, Enjalbart A, Kordon C, Rostene W (1985) Autoradiographic localization of a non-reducible somatostatin analog (125I-CGP-23996) binding sites in the rat brain: Comparison with membrane binding. Peptides 6:713–719Google Scholar
  32. Epelbaum J, Tapia-Arancibia L, Alonso G, Astier H, Kordon C (1986) The anterior periventricular hypothalamus is the site of somatostatin inhibition on its own release: An in vitro and immunohistochemical study. Neuroendocrinology 44:255–259Google Scholar
  33. Epelbaum J, Enjalbert A, Krantic S, Musset F, Bertrand P, Rasolonjanahary R, Shu C, Kordon C (1987) Somatostatin receptors on pituitary somatotrophs, thyrotrophs, and lactotrophs: pharmacological evidence for loose coupling to adenylate cyclase. Endocrinology 121:2177–2185Google Scholar
  34. Eppler C, Zijsk J, Corbet M, Shich H (1992) Purification of a pituitary receptor for somatostatin: The utility of biotinylated somatostatin analogs. J Biol Chem 267:15603–15612Google Scholar
  35. Eschalier A, Aumaitre O, Ardid D, Fialip J, Duchene-Marullaz P (1991) Long-lasting antinociceptive effect of RC-160, a somatostatin analog, in mice and rats. Eur J Pharmacol 199:119–121Google Scholar
  36. Evers M, Parekh D, Townsend CM (1991) Somatostatin and analogs in the treatment of cancer. Ann Surg 213:190–198Google Scholar
  37. Feniuk W, Dimech J, Humphrey PPA (1993) Characterization of somatostatin receptors in guinea-pig isolated ileum, vas deferens and right atrium. Br J Pharmacol 110:1156–1164Google Scholar
  38. Fosset M, Schmid-Antomarchi H, De Weille JR, Lazdunski M (1988) Somatostatin activates glibenclamide-sensitive and ATP-regulated K+ channels in insulinoma cells via a G-protein. FEBS Lett 242:94–96Google Scholar
  39. Fries JL, Murphy WA, Sueiras-Diaz, J, Coy DH (1982) Somatostatin antagonist analog increases GH, insulin, and glucagon release in the rat. Peptides 3:811–814Google Scholar
  40. Gonzalez BJ, Leroux P, Laquerrière Coy DH, Bodenant C, Vaudry H (1988) Transient expression of somatostatin receptors in the rat cerebellum during development. Brain Res Dev Brain Res 40:154–157Google Scholar
  41. Göthert M (1980) Somatostatin selectively inhibits noradrenaline release from hypothalamic neurones. Nature 288:86–88Google Scholar
  42. Haroutunian V, Mantin G, Campell G, Tsuboyama, G, Davis K (1987) Cysteamine-induced depletion of central SRIF-like immunoreactivity: effects on behavior, learning, memory and brain neurochemistry. Brain Res 403:234–242Google Scholar
  43. Heimann ML, Murphy WA, Coy DH (1987) Differential binding of somatostatin agonists to somatostatin receptors in brain and adenohypophysis. Neuroendocrinology 45:429–436Google Scholar
  44. Hoyer D, Clarke DE, Fozard JR, Hartig PR, Martin GR, Mylecharane EJ, Saxena PR, Humphrey PPA (1994a) International Union of Pharmacology Classification of receptors for 5-hydroxytryptamine (serotonin). Pharmacol Rev 42:157–204Google Scholar
  45. Hoyer D, Schoeffter P, Langenegger D, Kaupmann K, Lübbert H, Reubi JC, Bruns C (1994b) Pharmacological identity between somatostatin SS-1/SS-2 sites and SSTR-2/SSTR-1 receptors, respectively. Neuropeptides 29 (suppl 1):24Google Scholar
  46. Humphrey PPA, Hartig PR, Hoyer D (1993) A proposed new nomenclature for 5-HT receptors. Trends Pharmacol Sci 14:233–236CrossRefPubMedGoogle Scholar
  47. Ikeda SR, Schofield GG (1989) Somatostatin cyclic octapeptide analogs which preferentially bind to SOMa receptors block a calcium current in rat superior cervical ganglion neurons. Neurosci Lett 96:283–288Google Scholar
  48. Inoue M, Nakajima S, Nakajima Y (1988) Somatostatin induces an inward rectification in rat locus coeruleus neurones through a pertussis toxin-sensitive mechanism. J Physiol (Lond) 407:177–198Google Scholar
  49. Ipp E, Rivier J, Dobbs RE, Brown M, Vale W, Unger RH (1979) Somatostatin analogues inhibit somatostatin relase. Endocrinology 104:1270–1273Google Scholar
  50. Iversen LL, Iversen SD, Bloom F, Douglas C, Brown M, Vale W (1978) Calcium-dependent release of somatostatin and neurotensin from rat brain in vitro. Nature 273:161–163Google Scholar
  51. Jakobs K, Aktories K, Schultz G (1983) A nucleotide regulatory site for somatostatin inhibition of adenylate cyclase in S49 lymphoma cells. Nature 303:177–178Google Scholar
  52. Kaupmann K, Bruns C, Hoyer D, Seuwen K, Lübbert H (1993) mRNA distribution and second messenger coupling of four somatostatin receptors expressed in the brain. FEBS Lett 331:53–59Google Scholar
  53. Kenakin TP, Bond RA, Bonner TI (1992) Definition of pharmacological receptors. Pharmacol Rev 44:351–362Google Scholar
  54. Kleuss C, Hescheler J, Ewel C, Rosenthal W, Schultz G, Wittig B (1991) Assignment of G-protein subtypes to specific receptors inducing inhibition of calcium currents. Nature 353:43–48Google Scholar
  55. Kleuss C, Scherubl H, Hescheler J, Schultz G, Wittig B (1992) Different β-subunits determine G-protein interaction with transmembrane receptors. Nature 358:424–426Google Scholar
  56. Kleuss C, Scherubl H, Hescheler J, Schultz G, Wittig B (1993) Selectivity in signal transduction determined by γ-subunits of heterotrimeric G-proteins. Science 259:832–834Google Scholar
  57. Kluxen FW, Bruns C, Luebbert H (1992) Expression cloning of a rat brain somatostatin receptor cDNA. Proc Natl Acad Sci USA 89:4618–4622Google Scholar
  58. Koch BD, Schonbrunn A (1984) The somatostatin receptor is directly coupled to adenylate cyclase in GH4C1 pituitary cell membranes. Endocrinology 114:1784–1790Google Scholar
  59. Kong H, DePaoli A, Breder C, Yasuda K, Bell GI, Reisine T (1994) Differential expression of messenger RNAs for somatostatin receptor subtypes SSTR1, SSTR2, SSTR3 in adult rat brain: analysis by RNA blotting and in situ hybridization histochemistry. Neuroscience 59:175–184.Google Scholar
  60. Koop H, Eissele R, Kuhlkamp V, Bothe E, Dionysius J, Arnold R (1987) Calcitonin gene-related peptide stimulates rat gastric somatostatin release in vitro. Life Sci 40:541–546Google Scholar
  61. Lamberts SWJ, Hofland LJ, van Koetsveld P (1990) Parallel in vivo and in vitro detection of functional somatostatin receptors in human endocrine pancreatic tumors: Consequences with regard to diagnosis, localization and therapy. J Clin Endocrinol Metab 71:566–574Google Scholar
  62. Lamberts SWJ, Krenning EP, Reubi JC (1991) The role of somatostatin and its analogs in the diagnosis and treatment of tumors. Endocr Rev 12:450–482PubMedGoogle Scholar
  63. Law SF, Reisine T (1992) Agonist binding to rat brain somatostatin receptors alters the interaction of the receptors with guanine nucleotide-binding regulatory proteins. Mol Pharmacol 42:398–402Google Scholar
  64. Law SF, Manning D, Reisine, T (1991) Identification of the subunits of GTP-binding proteins coupled to somatostatin receptors. J Biol Chem 266:17885–17897Google Scholar
  65. Law SF, Yasuda K, Bell G, Reisine T (1993) Giα3 and G selectively associate with the cloned somatostatin receptor SSTR2. J Biol Chem 268:10721–10727Google Scholar
  66. Leroux P, Quirion R, Pelletier G (1985) Localization and characterization of brain somatostatin receptors as studied with somatostatin-14 and somatostatin-28 receptor autoradiography. Brain Res 347: 74–84Google Scholar
  67. Lewin MJM (1992) The somatostatin receptor in the GI tract. Annu Rev Physiol 54:455–468Google Scholar
  68. Lewis DL, Weight FF, Luini A (1986) A guanine nucleotide-binding protein mediates the inhibition of voltage-dependent calcium current by somatostatin in a pituitary cell line. Proc. Natl Acad Sci USA 83:9035–9039Google Scholar
  69. Li XJ, Forte M, North RA, Ross CA, Snyder SH (1992) Cloning and expression of a rat somatostatin receptor enriched in brain. J Biol Chem 267:21307–21312Google Scholar
  70. Markstein R, Stöckli KA, Reubi JC (1989) Differential effects of somatostatin on adenylate cyclase as functional correlate for different brain somatostatin receptor subpopulations. Neurosci Lett 104:13–18Google Scholar
  71. Marshall PE, Landis DMD (1985) Huntington's disease is accompanied by changes in the distribution of somatostatin-containing neuronal processes. Brain Res 329:71–82Google Scholar
  72. Martin JL, Chesselet MF, Raynor K, Gonzales C, Reisine T (1991) Differential distribution of somatostatin receptor subtypes in rat brain revealed by newly developed somatostatin analogs. Neuroscience 41:581–593Google Scholar
  73. Martin-Iversen MT, Radke JM, Vincent SR (1986) The effects of cysteamine on dopamine-mediated behaviors: evidence for dopamine-somatostatin interactions in the striatum. Pharmacol Biochem Behav 24:1707–1714Google Scholar
  74. Maton PN (1989) The use of the long-acting somatostatin analog, Octreotide acetate, in patients with islet cell tumors. Gastrointest Endocrinol S. 897–922Google Scholar
  75. Maurer R, Reubi JC (1985) Brain somatostatin receptor subpopulation visualized by autoradiography. Brain Res 333:178–181Google Scholar
  76. Meyer DK, Conzelmann U, Schultheiss K (1989) Effects of somatostatin-14 on the in vitro release of [3H]GABA from slices of rat caudate putamen. Neuroscience 28:61–68Google Scholar
  77. Meyerhof W, Wulfsen I, Schonrock C, Fehr S, Richter D (1992) Molecular cloning of a somatostatin-28 receptor and comparison of its expression pattern with that of a somatostatin-14 receptor in rat brain. Proc Natl Acad Sci USA 89:10267–10271Google Scholar
  78. Meyers CA, Kastin AJ, Schally AV, Coy DH (1981) Use of the mouse vas deferens assay to evaluate the action of somatostatin peptides on gastric acid secretion. Digestion 21:21–24Google Scholar
  79. Mihara S, North RA, Surprenant A (1987) Somatostatin increases an inwardly rectifying potassium conductance in guineapig submucous plexus neurones. J Physiol (Lond) 390:335–355Google Scholar
  80. Moore SD, Madamba SG, Joels M, Siggins GR (1988) Somatostatin augments the M-current in hippocampal neurons. Science 239:278–280Google Scholar
  81. Nemeth EF, Cooper JR (1979) Effect of somatostatin on acetylcholine release from rat hippocampal synaptosomes. Brain Res 165: 166–170Google Scholar
  82. O'Carroll AM, Lolait SJ, Konig M, Mahan LC (1992) Molecular cloning and expression of a pituitary somatostatin receptor with preferential affinity for somatostatin-28. Mol Pharmacol 42:939–946Google Scholar
  83. O'Dorisio TM, Redfern JS (1990) Somatostatin and somatostatin-like peptides: Clinical research and clinical applications. Adv Endocrinol Metab 1:175–230Google Scholar
  84. Palacios JM, Rigo M, Chinaglia G, Probst A (1990) Reduced density of somatostatin receptors in Huntington's chorea. Brain Res 522: 342–346Google Scholar
  85. Patel YC, Srikant CB (1986) Somatostatin mediation of adenohypophysial secrretion. Annu Rev Physiol 48:551–567Google Scholar
  86. Patel YC, Greenwood M, Kent G, Panetta R, Srikant CB (1993) Multiple gene transcripts of the somatostatin receptor SSTR2: tissue selective distribution and cAMP regulation. Biochem Biophys Res Commun 192:288–94Google Scholar
  87. Patel YC, Greenwood MT, Warszynska A, Panetta, R, Srikant CB (1994) All five cloned human somatostatin receptors (hSSTR1–5) are functionally coupled to adenylyl cyclase. Biochem Biophys Res Commun 198:605–612Google Scholar
  88. Perez J, Hoyer D (1994) Coexpression of somatostatin SSTR-4 and SSTR-3 receptor mRNAs in the rat central nervous system. Neuroscience, submittedGoogle Scholar
  89. Perez J, Rigo M, Kaupmann K, Bruns C, Yasuda K, Bell GI, Lübbert H, Hoyer D (1994) Localisation of somatostatin (SRIF) SSTR-1, SSTR-2 and SSTR-3 receptor mRNA in rat brain by in situ hybridization. Naunyn Schmiedebergs Arch Pharmacol 349:145–160Google Scholar
  90. Priestley T, Woodruff GN (1988) The inhibitory effect of somatostatin peptides on the rat anococcygeus muscle in vitro. Br J Pharmacol 94:87–96Google Scholar
  91. Quirion R, Regoli D, Rioux F, St-Pierre S (1979) An analysis of the negative inotropic action of somatostatin. Br J Pharmacol 66:251–257Google Scholar
  92. Raynor K, Reisine T (1989) Analogs of somatostatin selectively label distinct subtypes of somatostatin receptors in rat brain. J Pharmacol Exp Ther 251:510–517Google Scholar
  93. Raynor K, Wang HL, Dichter M, Reisine T (1991) Subtypes of brain somatostatin receptors couple to multiple cellular effector systems. Mol Pharmacol 40:248–253Google Scholar
  94. Raynor K, Murphy WA, Coy DH, Taylor JE, Moreau J-P, Yasuda K, Bell GI, Reisine T (1993a) Cloned somatostatin Receptors: Identification of subtype-selective peptides and demonstration of high affinity binding of linear peptides. Mol Pharmacol 43:838–844Google Scholar
  95. Raynor K, O'Carroll A-M, Kong H, Yasuda K, Mahan LC, Bell GI, Reisine T (1993b) Characterization of cloned somatostatin receptors. Mol Pharmacol 44:385–392Google Scholar
  96. Raynor K, Lucki I, Reisine T (1993c) Somatostatin receptors in the nucleus accumbens selectively mediate the stimulatory effect of somatostatin on locomotor activity in rats. J Pharmacol Exp Ther 265 (1):67–73Google Scholar
  97. Reichlin S (1983) Somatostatin. N Engl J Med 309:1495–1505; 1556–1563Google Scholar
  98. Reisine T (1990) Cellular mechanisms of somatostatin inhibition of calcium influx in the anterior pituitary cell line AtT-20. J Pharmacol Exp Ther 254:646–651Google Scholar
  99. Reisine T, Zhang Y, Sekura R (1985) Pertussis toxin treatment blocks the inhibition of somatostatin and increases stimulation by forskolin of cAMP accumulation and adrenocorticotropin secretion from mouse anterior pituitary cells. J Pharmacol Exp Ther 232:275–282Google Scholar
  100. Reisine T, Kong H, Raynor K, Yano H, Takeda J, Yasuda K, Bell GI (1993) Splice variant of the somatostatin receptor 2 subtype, SSTR2B, couples to adenylyl cyclase. Mol Pharmacol 44: 1016–1020Google Scholar
  101. Rens-Domiano S, Law SF, Yamada Y, Seino S, Bell GI, Reisine T (1992) Pharmacological properties of two cloned somatostatin receptors. Mol Pharmacol 42:28–34Google Scholar
  102. Reubi JC, (1984) Evidence for two somatostatin-14 receptor types in rat brain cortex. Neurosci Lett 49:259–263Google Scholar
  103. Reubi JC (1985) New specific radioligand for one subpopulation of brain somatostatin receptors. Life Sci 36:1829–1836Google Scholar
  104. Reubi JC, Maurer R (1985) Autoradiographic mapping of somatostatin receptors in the rat central nervous system and pituitary. Neurosci 15:1183–1193Google Scholar
  105. Reubi JC, Maurer R (1986) Different ionic requirements for somatostatin receptor subpopulations in the brain. Regul Pept 14:301–311Google Scholar
  106. Reubi JC, Perrin M, Rivier J, Vale W (1982a) High affinity binding sites for somatostatin to rat pituitary. Biochem Biophys Res Commun 105:1538–1545Google Scholar
  107. Reubi JC, Rivier J, Perrin M, Brown M, Vale W (1982b) Specific high affinity binding sites for somatostatin-28 on pancreatic β-cells: differences with brain somatostatin receptors. Endocrinology 110: 1049–1050Google Scholar
  108. Reubi JC, Cortès R, Maurer R, Probst A, Palacios JM (1986) Distribution of somatostatin receptors in the human brain: an autoradiographic study. Neuroscience 18:329–346Google Scholar
  109. Reubi JC, Probst A, Cortes R, Palacios JM (1987) Distinct topographical localization of two somatostatin receptor subpopulations in the human cortex. Brain Res 4406:391–396Google Scholar
  110. Reubi JC, Krenning EP, Lamberts SWJ, Kvols L (1993) In vitro detection of somatostatin receptors in human tumors. Digestion 54 (Suppl 1):76–83Google Scholar
  111. Rivier J, Brown M, Vale W (1975) D-Trp-8-somatostatin: an analog of somatostatin more potent than the native molecule. Biochem Biophys Res Commun 65:746–751Google Scholar
  112. Robbins RJ, Landon RM (1983) Somatostatin release from cerebral cortical cells: influence of amino acid neurotransmitters. Brain Res 273:374–378Google Scholar
  113. Rohrer L, Raulf F, Bruns C, Buettner R, Hofstaedter F, Schuele R (1993) Cloning and characterisation of a novel human somatostatin receptor. Proc Natl Acad Sci USA 90:4196–4200Google Scholar
  114. Rosenthal W Hescheler J, Hinsch K-D, Spicher K, Trautwein W Schultz G (1988) Cyclic AMP-independent dual regulation of voltage-dependent Ca2+ currents by LHRH and somatostatin in a pituitary cell line. EMBO 7:1627–1633Google Scholar
  115. Schonbrunn A, Tashjian AH (1978) Characterization of functional receptors for somatostatin in rat pituitary cells in culture. J Biol Chem 253:6473–6483Google Scholar
  116. Schweitzer P, Madamba S, Champagnat J, Siggins GR (1993) Somatostatin inhibition of hippocampal CAI pyramidal neurons: mediation by arachidonic acid and its metabolites. J Neurosci 13: 2033–49Google Scholar
  117. Sims SM, Lussier BT, Kraicer J (1991) Somatostatin activates an inwardly rectifying K+ conductance in freshly dispersed rat somatotrophs. J Physiol (Lond) 441:615–637Google Scholar
  118. Srikant CB, Patel YC (1981a) Somatostatin receptors: Identification and characterization in rat membranes. Proc Natl Acad Sci USA 78:3930–3934Google Scholar
  119. Srikant CB, Patel YC (1981b) Somatostatin Analogs. Dissociation of brain receptor binding affinities and pituitary actions in the rat. Endocrinology 108:341–343Google Scholar
  120. Srikant CB, Patel YC (1981c) Receptor binding of somatostatin-28 is tissue specific. Nature 294:259–260Google Scholar
  121. Srikant CB, Patel YC (1986) Somatostatin receptors on rat pancreatic acinar cells. J Biol Chem 86:7690–7696Google Scholar
  122. Srikant CB, Patel YC (1987) Somatostatin receptor: evidence for structural and functional heterogeneity. In: Reichlin S (ed) Somatostatin Basic and Clinical Aspects. Plenum Press, New York, pp 89–103Google Scholar
  123. Strnad J, Eppler CM, Corbet M, Hadcock JR (1993) The rat SSTR2 somatostatin receptor subtype is coupled to inhibition of cyclic AMP accumulation. Biochem Biophys Res Commun 191:968–976Google Scholar
  124. Tanaka S, Tsujimoto A (1981) Somatostatin facilitates the serotonin release form rat cerebral cortex, hippocampus and hypothalamus slices. Brain Res 208:219–222Google Scholar
  125. Tapia-Arancibia L, Astier H (1988) Glutamate stimulates somatostatin release from diencephalic neurons in primary culture. Endocrinology 123:2360–2366Google Scholar
  126. Tapia-Arancibia L, Astier H (1990) Pharmacological properties of the NMDA receptor involved in somatostatin release from cortical neurons. Eur J Pharmacol 186:319–322Google Scholar
  127. Thermos K, Reisine T (1988) Somatostatin receptor subtypes in the clonal anterior pituitary cell lines AtT-20 and GH3. Mol Pharmacol 33:370–377Google Scholar
  128. Tran V, Beal F, Martin J (1985) Two types of somatostatin receptors differentiated by cyclic somatostatin analogs. Science 228:492–495Google Scholar
  129. Uhl GR, Tran V, Snyder SH, Martin JB (1985) Somatostatin receptors: distribution in rat central nervous system and human frontal cortex. J Comp Neurol 240:228–304Google Scholar
  130. Unger JW McNeill TH, Lapham LL, Hamill RW (1988) Neuropeptides and neuropathology in the amygdala in Alzheimer's disease: relationship between somatostatin, neuropeptide Y and subregional distribution of neuritic plaques. Brain Res 452:293–302Google Scholar
  131. Vale W, Rivier C, Brazeau P, Guillemin R (1974) Effects of somatostatin on the secretion of thyrotropin and prolactin. Endocrinology 95:968–977Google Scholar
  132. Vanetti M, Kouba M, Wang X, Vogt G, öllt V (1992) Cloning and expression of a novel mouse somatostatin receptor (SSTR2B). FEBS Lett 311:290–294Google Scholar
  133. Vanetti M, Vogt G, Höllt V (1993) The two isoforms of the mouse somatostatin receptor (mSSTR2A and mSSTR2B) differ in coupling efficiency to adenylate cyclase and agonist-induced receptor desensitization. FEBS Lett 331:260–266Google Scholar
  134. Veber DF, Holly FW, Nutt RF, Bergstrand SJ, Brady SF, Hirschmann R, Glitzer MS, Saperstein R (1979) Highly active cyclic and bicyclic somatostatin analogues of reduced ring size. Nature 280:512–514Google Scholar
  135. Veber DF, Freidinger RM, Perlow DS, Paleveda WJ, Holly FW, Strachan RG, Nutt RF, Arison BH, Homnick C, Randall WC, Glitzer MS, Saperstein R, Hirschmann R (1981) A potent cyclic hexapeptide analogue of somatostatin. Nature 292:55–58Google Scholar
  136. Vecsei L, Widerlov E (1990) Preclinical and clinical studies with somatostatin related to the central nervous system. Prog Neuropsychopharmacol Biol Psychiatry 14:473–502Google Scholar
  137. Vezzani A, Serafini R, Stasi MA, Vigano G, Rizzi M, Samanin (1991) A peptidase resistant cyclic octapeptide analogue of somatostatin (SMS 201–995) modulates seizures induced by quinolinic and kainic acids differentially in the rat hippocampus. Neuropharmacology 30:345–352Google Scholar
  138. Vezzani A, Monno A, Rizzi M, Galli A, Barrios M, Samanin R (1992) Somatostatin release is enhanced in the hippocampus of partially and fully kindled rats. Neuroscience 51:41–46Google Scholar
  139. Vezzani A, Ruiz R, Monno A, Rizzi M, Lindenfors N, Samanin R, Brodin E (1993) Extracellular somatostatin measured by microdialysis in the hippocampus of freely moving rats: evidence for neuronal release. J Neurochem 60:671–677Google Scholar
  140. Viguerie N, Tahiri-Jouti N, Esteve JP, Clerc P, Logsdon C, Svoboda M, Susini C, Vaysse N, Riberet A (1988) Functional somatostatin receptors on a rat pancreatic acinar cell line. Am J Physiol 255:G113-G120Google Scholar
  141. Wang H-L, Bogen C, Reisine T, Dichter M (1989) Somatostatin-14 and somatostatin-28 induce opposite effects on potassium currents in rat neocortical neurons. Proc Natl Acad Sci USA 86:9616–9620Google Scholar
  142. Wang H-L, Dichter M, Reisine T (1990) Lack of cross-desensizization of somatostatin-14 and somatostatin-28 receptors coupled to potassium channels in rat neocortical neurons. Mol Pharmacol 38:357–361Google Scholar
  143. Watson TWJ, Pittman QJ (1988) Pharmacological evidence that somatostatin activates the M-current in hippocampal pyramidal neurons. Neurosci Lett 91:172–176Google Scholar
  144. White RE, Schonbrunn A, Armstrong DL (1991) Somatostatin stimulates Ca2+-activated K+ channels through protein dephosphorylation. Nature 351:570–573Google Scholar
  145. Wulfsen I, Meyerhof W, Fehr S, Richter D (1993) Expression patterns of rat somatostatin receptor genes in pre- and postnatal brain and pituitary. J Neurochem 61: 1549–1552Google Scholar
  146. Xu Y, Song J, Bruno JF, Berelowitz M (1993) Molecular cloning and sequencing of a human somatostatin receptor, hSSTR4. Biochem Biophys Res Commun 193:648–652Google Scholar
  147. Yamada Y, Post SR, Wang K, Tager HS, Bell GI, Seino S (1992a) Cloning and functional characterization of a family of human and mouse somatostatin receptors expressed in brain, gastrointestinal tract, and kidney. Proc Natl Acad Sci USA 89:251–255Google Scholar
  148. Yamada Y, Reisine T, Law SF, Yu I, Kubota A, Kagimoto S, Seino M, Seino Y, Bell GI, Seino S (1992b) Somatostatin receptors, an expanding gene family: Cloning and functional characterization of human SSTR3, a protein coupled to adenylyl cyclase. Mol Endocrinol 6:2136–2142Google Scholar
  149. Yamada Y, Stoffel M, Espinosa R III, Xiang K-S, Seino M, Seino S, Le Beau M, Bell GI, (1993a) Human somatostatin receptor genes: localization to human chromosomes 14, 17 and 22 and identification of simple tandem repeat polymorphisms. Genomics 15:449–452Google Scholar
  150. Yamada Y, Kagimoto S, Kubota A, Yasuda K, Masuda K, Someya Y, Ihara, Y, Li Q, Seino M, Seino S, (1993b) Cloning, functional expression and pharmacological characterization of a fourth (hSSTR4) and fifth (hSSTR5) human somatostatin receptor subtype. Biochem Biophys Res Commun 195:844–852Google Scholar
  151. Yasuda K, Rens-Domiano S, Breder CD, Law SF, Saper CB, Reisine T, Bell GI (1992) Cloning of a novel somatostatin receptor, SSTR3, coupled to adenylylcyclase. J Biol Chem 267:20422–20428Google Scholar
  152. Yatani A, Codina J, Sekura R, Birnbaumer L, Brown A (1987) Reconstitution of somatostatin and muscarinic receptor mediated stimulation of K+ channels by isolated Gk protein in clonal rat anterior pituitary cell membranes. Mol Endocrinol 1:283–289Google Scholar

Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • Daniel Hoyer
    • 1
  • Hermann Lübbert
    • 1
  • Christian Bruns
    • 1
  1. 1.Preclinical Research, 360/604Sandoz Pharma Ltd.BaselSwitzerland

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