Skip to main content
Log in

Regulation der Azinuszellrezeptoren des Pankreas durch Peptide

Regulation of pancreatic acinar receptors by peptides

  • Übersichten
  • Published:
Klinische Wochenschrift Aims and scope Submit manuscript

Summary

Peptides may act on the same receptor they regulate or on another receptor by causing regulations via receptor interactions. These receptor regulations include changes of receptor affinity and capacity. Receptor capacity is regulated by internalization, recycling, degradation, synthesis, and modification of bioavailability without migration of the receptor. Examples for those regulations, mostly based on experiments with isolated pancreatic acini from the rat, mouse, or guinea pig, are given.

For the CCK receptor these examples include complex regulations of this receptor by CCK itself, bringing into discussion the hypothesis of negative cooperativity and the two-site receptor model, desensitization of the receptor by CCK, in vivo CCK influences on its receptor, and insulin receptor/CCK receptor interactions. For the insulin receptor the physiological significance of “up and down regulation” of this receptor by insulin itself is discussed. For the IGF receptors and the EGF receptor CCK-induced, Ca2+-mediated regulation of receptor internalization are another type of regulation with unknown physiological and pathophysiological significance. Finally CCK-induced, Ca2+-mediated regulation of somatostatin receptor capacity and affinity are mentioned.

It is postulated that those regulations play an important role in influencing the biological effect of hormones and that knowledge about them may improve our understanding of pathophysiology.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

CCK:

Cholecystokinin

IGF:

insulin like growth factor

mRNA:

messenger-Ribonukleinsäure

MW:

Molekulargewicht

VIP:

vasoactive intestinal peptide

Literatur

  1. Abdelmoumene S, Gardner JD (1980) Cholecystokinin-induced desensitization of enzyme secretion in dispersed acini from guinea pig pancreas. Am J Physiol 239:G272-G279

    CAS  PubMed  Google Scholar 

  2. Bergeron JJM, Rachubinski R, Searle N, Sikstrom R, Borts D, Bastian P, Posner BI (1980) Radioautographic visualization of in vivo insulin binding to the exocrine pancreas. Endocrinology 107:1069–1080

    Article  CAS  PubMed  Google Scholar 

  3. Berridge MJ (1983) Rapid accumulation of inositol trisphosphate reveals that agonists hydrolyse polyphosphoinositides instead of phosphotidylinositol. Biochem J 212:849–858

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Burgess GM, Godfrey PP, McKinney JS, Berridge MJ, Irvine RF, Putney JW jr (1984) The second messenger linking receptor activation of internal Ca2+ release in liver. Nature 307:63–66

    Article  Google Scholar 

  5. Christophe JP, Colon TP, Gardner JD (1976) Interaction of porcine vasoactive intestinal peptide with dispersed pancreatic acinar cells from the guinea pig. Binding of radioiodinated peptide. J Biol Chem 251:4629–4634

    CAS  PubMed  Google Scholar 

  6. Dagorn JC, Lahaie RG (1981) Dietary regulation of pancreatic protein synthesis. I rapid and specific modulation of enzyme synthesis by changes in dietary composition. Biochim Biophys Acta 654:111–118

    Article  CAS  PubMed  Google Scholar 

  7. DeMeyts P, Roth J, Neville DM jr, Gavin JR, Lesniak A (1973) Insulin interaction with its receptors: experimental evidence for negative cooperativity. Biochem Biophys Res Commun 55:154–161

    Article  CAS  Google Scholar 

  8. Erspamer V, Fakonieri Erspamer G, Inselvini M, Negri L (1972) Occurrence of bombesin and alytensin in extracts of the skin of three European discoglossid frogs and pharmacological actions of bombesin on extracellular smooth muscle. Br J Pharmacol 45:333–348

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Esteve JP, Vaysse N, Susini C, Kunsch JM, Fourmy D, Pradayrol L, Wünsch E, Moroder L, Ribet A (1983) Bimodal regulation of pancreatic exocrine function in vitro by somatostatin-28. Am J Physiol 245:G208-G216

    CAS  PubMed  Google Scholar 

  10. Esteve JP, Susini C, Vaysse N, Antoniotti H, Wünsch E, Berthon G, Ribet A (1984) Binding of somatostatin to pancreatic acinar cells. Am J Physiol 247:G62-G69

    CAS  PubMed  Google Scholar 

  11. Fujita-Yamaguchi Y, Choi S, Sakamoto Y, Itakura K (1983) Purification of insulin receptor with full binding activity. J Biol Chem 258:5045–5049

    CAS  PubMed  Google Scholar 

  12. Gardner JD, Conlon TP, Adams TD (1976) Cyclic AMP in pancreatic acinar cells: effects of gastrointestinal hormones. Gastroenterology 70:29–35

    CAS  PubMed  Google Scholar 

  13. Gardner JD, Rottman AJ (1979a) Action of cholera toxin on dispersed acini from guinea pig pancreas. Biochim Biophys Acta 585:250–265

    Article  CAS  PubMed  Google Scholar 

  14. Gardner JD, Rottman AJ, Natarajan S, Bodanszky M (1979b) Interaction of secretin5–27 and its analogues with hormone receptors on pancreatic acini. Biochim Biophys Acta 583:491–503

    Article  CAS  PubMed  Google Scholar 

  15. Gardner JD, Jensen RT (1980) Receptors for secretagogues on pancreatic acinar cells. Am J Physiol 238:G63-G66

    CAS  PubMed  Google Scholar 

  16. Gardner JD, Jensen RT (1982) Receptor modulation of calcium and cyclic AMP: differences in coupling to specific hormone-receptor complexes in cells responsive to several hormones. In: Hormone Receptors. S 277–308, John Wiley and Sons, Ltd, Hrsg Kohn LD

  17. Gardner JD, Jensen RT (1983) Gastrointestinal peptides: the basis of action at the cellular level. Rec Prog Horm Res 39:211–243

    CAS  PubMed  Google Scholar 

  18. Gavin JR, Roth J, Neville DM jr, DeMeyts P, Buell DN (1974) Insulin-dependent regulation of insulin receptor concentrations. A direct demonstration in cell culture. Proc Natl Acad Sci USA 71:84–88

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Gill GN, Kawamoto T, Cochet C, Le A, Sato JD, Masui H, McLeod C, Mendelson J (1984) Monoclonal anti-epidermal growth factor receptor antibodies which are inhibitors of epidermal growth factor binding and antagonists of epidermal growth factor stimulated tyrosine protein kinase activity. J Biol Chem 259:7755–7760

    CAS  PubMed  Google Scholar 

  20. Goldfine ID, Clawson GA, Smuckler EA, Purello F, Vigneri R (1982) Action of insulin at the nuclear envelope. Mol Cell Biochem 48:3–14

    Article  CAS  PubMed  Google Scholar 

  21. Goldfine ID, Williams JA (1983) Receptors for insulin and CCK in the acinar pancreas. Relationship to hormone action. Int Rev Cyt 85:1–38

    Article  CAS  Google Scholar 

  22. Grossman MI, Greengard M, Ivy AC (1942) The effect of dietary composition on pancreatic enzymes. Am J Physiol 138:676–682

    Google Scholar 

  23. Hedo JA, Simpson IA (1984) Internalization of insulin receptors in the isolated rat adipose cell. Demonstration of the vectorial disposition of receptor subunits. J Biol Chem 259:11083–11089

    CAS  PubMed  Google Scholar 

  24. Jacobs S, Cuatrecasas P (1981) Insulin receptor: structure and function. Endocr Rev 2/3:251–261

    Article  Google Scholar 

  25. Jensen RT, Moody T, Pert C, Rivier JE, Gardner JD (1978) Interaction of bombesin and litorin with specific membrane receptors on pancreatic acinar cells. Proc Natl Acad Sci USA 75:6139–6143

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Jensen RT, Gardner JD (1979) Interaction of physalaemin, substance P, and eledoisin with specific membrane receptors on pancreatic acinar cells. Proc Natl Acad Sci USA 78:5679–5683

    Article  Google Scholar 

  27. Jensen RT, Tatemoto K, Mutt V, Lemp GF, Gardner JD (1981) Actions of a newly isolated intestinal peptide PHI on pancreatic acini. Am J Physiol 241:G498-G502

    CAS  PubMed  Google Scholar 

  28. Jensen RT, Charlton CG, Adachi H, Jones SW, O'Dondrue TL, Gardner JD (1983) Use of125I-secretin to identify and characterize high-affinity secretin receptors on pancreatic acini. Am J Physiol 245:G186-G195

    CAS  PubMed  Google Scholar 

  29. Jensen RT, Gardner JD (1984) Receptors for secretagogues on pancreatic acinar cells. J Ped Gastroenterol Nutr 3 (Suppl 1):25–35

    Article  CAS  Google Scholar 

  30. Kasuga M, van Obberghen E, Nissley SP, Rechler MM (1981) Demonstration of two subtypes of insulin-like growth factor receptors by affinity crosslinking. J Biol. Chem 256:5305–5308

    CAS  PubMed  Google Scholar 

  31. Korc M, Matrisian LM, Planck SR, Magun BE (1983) Binding of epidermal growth factor in rat pancreatic acini. Biochim Biophys Res Comm 111:1066–1073

    Article  CAS  Google Scholar 

  32. Korc M, Matrisian LM, Magun BE (1984) Cytosolic calcium regulates epidermal growth factor endocytosis in rat pancreas and cultured fibroblasts. Proc Natl Acad Sci USA 81:461–465

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Larose J, Dumont Y, Asselin J, Morisset J, Poirier GG (1981) Muscarinic receptor of rat pancreatic acini: [3H] QNB binding and amylase secretion. Europ J Pharmacol 76:247–254

    Article  CAS  Google Scholar 

  34. Lee PC, Jensen RT, Gardner JD (1980) Bombesin-induced desensitization of enzyme secretion in dispersed acini from guinea pig pancreas. Am J Physiol 238:G213-G218

    CAS  PubMed  Google Scholar 

  35. Logsdon CD, Williams JA (1983) Epidermal growth factor binding and biologic effects on mouse pancreatic acini. Gastroenterology 85:339–345

    CAS  PubMed  Google Scholar 

  36. Logsdon CD, Williams JA (1984) Intracellular Ca2+ and phorbol esters synergistically inhibit internalization of epidermal growth factor in pancreatic acini. Biochem J 223:893–900

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Massague J, Czech MP (1982) The subunit structures of two distinct receptors for insulin-like growth factors I and II and their relationship to the insulin receptor. J Biol Chem 257:5038–5045

    CAS  PubMed  Google Scholar 

  38. Mössner J, Logsdon CD, Potau N, Williams JA, Goldfine ID (1984a) Effect of intracellular Ca2+ on insulin-like growth factor II internalization into pancreatic acini. Roles of insulin and cholecystokinin. J Biol Chem 259:12350–12356

    PubMed  Google Scholar 

  39. Mössner J, Logsdon CD, Goldfine ID, Williams JA (1984b) Regulation of pancreatic acinar cell insulin receptors by insulin. Am J Physiol 247:G155-G160

    PubMed  Google Scholar 

  40. Mössner J, Roach E, Goldfine ID, Williams JA (1985) Electron microscopic autoradiographic studies of insulin and insulin like growth factor II uptake into pancreatic acini. Digestion 32:1244

    Google Scholar 

  41. Ng KH, Morisset J, Poirier GG (1979) Muscarinic receptors of the pancreas: a correlation between displacement of [3H]-quinuclidinyl benzilate binding and amylase secretion. Pharmacol 18:263–270

    Article  CAS  Google Scholar 

  42. Nishizuka Y (1984) Turnover of inositol phospholipids and signal transduction. Science 225:1365–1370

    Article  CAS  PubMed  Google Scholar 

  43. Otsuki M, Williams JA (1983a) Direct modulation of pancreatic CCK receptors and enzyme secretion by insulin in isolated pancreatic acini from diabetic rats. Diabetes 32:241–246

    Article  CAS  PubMed  Google Scholar 

  44. Otsuki M, Williams JA (1983b) Amylase secretion by isolated pancreatic acini after chronic cholecystokinin treatment in vivo. Am J Physiol 244:G683-G688

    CAS  PubMed  Google Scholar 

  45. Otsuki M, Okabayashi Y, Ohki A, Hootman SR, Baba S, Williams JA (1984a) Amylase secretion by isolated pancreatic acini after acute cholecystokinin treatment in vivo. Am J Physiol 246:G419-G425

    CAS  PubMed  Google Scholar 

  46. Otsuki M, Goldfine ID, Baba S, Williams JA (1984b) Diabetes in the rat is associated with a reversible post receptor defect in cholecystokinin action. Gasteroenterology 87:882–887

    CAS  Google Scholar 

  47. Pandol SJ, Jensen RT, Gardner JD (1982) Mechanism of [Tyr4]bombesin-induced desensitization in dispersed acini from guinea pig pancreas. J Biol Chem 257:12024–12029

    CAS  PubMed  Google Scholar 

  48. Potau N, Mössner J, Williams JA, Goldfine ID (1984) Cholecystokinin and insulin regulate insulin-like growth factor II binding to pancreatic receptors; evidence of a role for intracellular calcium. Biochem Biophys Res Commun 119:359–364

    Article  CAS  PubMed  Google Scholar 

  49. Sakamoto C, Goldfine ID, Williams JA (1984) The somatostatin receptor on isolated pancreatic acinar cell plasma membranes: identification of subunit structure and direct regulation by cholecystokinin. J Biol Chem 259:9623–9627

    CAS  PubMed  Google Scholar 

  50. Sankaran H, Goldfine ID, Deveney CW, Wong KY, Williams JA (1980) Binding of cholecystokinin to high affinity receptors on isolated rat pancreatic acini. J Biol Chem 255:1849–1853

    CAS  PubMed  Google Scholar 

  51. Sankaran H, Iwamoto Y, Korc M, Williams JA, Goldfine ID (1981) Insulin action in pancreatic acini from streptozotozin-treated rats. II. Binding of125I-insulin to receptors. Am J Physiol 240:G63-G68

    CAS  PubMed  Google Scholar 

  52. Sankaran H, Goldfine ID, Bailey A, Licko V, Williams JA (1982) Relationship of cholecystokinin receptor binding to regulation of biological functions in pancreatic acini. Am J Physiol 242:G250-G257

    CAS  PubMed  Google Scholar 

  53. Stöckmann F, Söling HD (1981) Regulation of biosynthesis of trypsinogen and chymotrypsinogen by nutrional and hormonal factors in the rat. Eur J Clin Invest 11:121–132

    Article  PubMed  Google Scholar 

  54. Streb H, Irvine RF, Berridge MJ, Schulz I (1983) Release of Ca2− from a nonmitochondrial intracellular store in pancreatic acinar cells by inositol-1,4,5-trisphosphate. Nature 306:67–68

    Article  CAS  PubMed  Google Scholar 

  55. Ullrich A, Coussens L, Hayflick JS, Dull TJ, Gray A, Tam AW, Lee J, Yareden Y, Libermann TA, Schlessinger J, Downward J, Mayes ELV, Whittle N, Waterfield MD, Seeburg PH (1984) Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A 431 epidermoid carcinoma cells. Nature 309:419–425

    Article  Google Scholar 

  56. Ullrich A, Bell JR, Chen EY, Herrera R, Petruzelli LM, Dull TJ, Gray A, Coussens L, Liao Y-C, Tsubokawa M, Mason A, Seeburg PH, Grunfeld C, Rosen OM, Ramachandran J (1985) Human insulin receptor and its relationship to the tyrosine kinase family of oncogenes. Nature 313:756–761

    Article  CAS  PubMed  Google Scholar 

  57. van Obberghen E, Kasuga M, Le Cam A, Hedo JA, Hiu A, Harrison LC (1981) Biosynthetic labeling of insulin receptor: studies of subunits in cultured IM-9 lymphocytes. Proc Natl Acad Sci USA 78:1052–1055

    Article  PubMed  PubMed Central  Google Scholar 

  58. van Obberghen E, Rossi B, Kowalski A, Gazzano H, Ponzio G (1983) Receptor-mediated phosphorylation of the hepatic insulin receptor: evidence that the Mr 95000 receptor subunit is its own kinase. Proc Natl Acad Sci USA 80:945–949

    Article  PubMed  PubMed Central  Google Scholar 

  59. Wicker C, Puigserver A, Scheele G (1984) Dietary regulation of levels of active mRNA coding for amylase and serine protease zymogens in the rat pancreas. Eur J Biochem 139:381–387

    Article  CAS  PubMed  Google Scholar 

  60. Williams JA, Korc M, Dormer RL (1978) Action of secretagoues on a new preparation of functionally intact, isolated pancreatic acini. Am J Physiol 235:E517-E524

    CAS  Google Scholar 

  61. Williams JA, Sankaran H, Korc M, Goldfine ID (1981) Receptors for cholecystokinin and insulin in isolated pancreatic acini: hormonal control of secretion and metabolism. Fed Proc 40:2497–2502

    CAS  PubMed  Google Scholar 

  62. Williams JA, Bailey A, Humbel R, Goldfine ID (1984) Insulin-like growth factors (IGF) bind to specific receptors in isolated pancreatic acini. Am J Physiol 246:G96-G99

    CAS  PubMed  Google Scholar 

  63. Yarden Y, Harari I, Schlessinger J (1985) Purification of an active EGF receptor kinase with monoclonal antireceptor antibodies. J Biol Chem 260:315–319

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mössner, J., Fischbach, W. Regulation der Azinuszellrezeptoren des Pankreas durch Peptide. Klin Wochenschr 64, 489–498 (1986). https://doi.org/10.1007/BF01713055

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01713055

Key words

Navigation