Galanin pp 113-131 | Cite as

Neurochemical Modulation of Central Cardiovascular Control: The Integrative Role of Galanin

  • Zaida Díaz-Cabiale
  • Concepción Parrado
  • Manuel Narváez
  • Carmelo Millón
  • Araceli Puigcerver
  • Kjell Fuxe
  • José Angel Narváez
Chapter
First Online:
Part of the Experientia Supplementum book series (EXS, volume 102)

Abstract

Galanin (GAL) is a peptide involved in multiple functions, including central cardiovascular control. In this review, the role of GAL and its fragments in the modulation of cardiovascular neuronal networks in the nucleus of the solitary tract is presented, including its interaction with the classical neurotransmitters and other neuropeptides involved in cardiovascular responses in this nucleus. First, we describe the cardiovascular responses of GAL and the pathway involved in these responses. Then we summarize findings obtained in our laboratory on how GAL, through its receptors, interacts with two other neuropeptides – Neuropeptide Y and Angiotensin II and their receptors – as they have particularly conspicuous cardiovascular effects. All these results strengthen the role of GAL in central cardiovascular control and indicate the existence of interactions among GAL receptor subtypes and α2-adrenergic receptors, AT1, and Y1 receptor subtypes. These interactions are crucial for understanding the integrative mechanisms responsible for the organization of the cardiovascular responses from the NTS.

Keywords

Galanin fragments NTS Cardiovascular control Angiotensin II NPY 
This is a preview of subscription content, log in to check access.

Notes

Acknowledgments

This study was supported by Spanish DGCYT BFI2008-3369 and SEJ01323.

References

  1. 1.
    Spyer KM (1981) Neural organisation and control of the baroreceptor reflex. Rev Physiol Biochem Pharmacol 88:24–124PubMedGoogle Scholar
  2. 2.
    Dampney RA (1994) Functional organization of central pathways regulating the cardiovascular system. Physiol Rev 74:323–364PubMedCrossRefGoogle Scholar
  3. 3.
    Singewald N, Philippu A (1996) Involvement of biogenic amines and amino acids in the central regulation of cardiovascular homeostasis. Trends Pharmacol Sci 17:356–363PubMedGoogle Scholar
  4. 4.
    Palkovits M, Mezey E, Fodor M, Ganten D, Bahner U, Geiger H et al (1995) Neurotransmitters and neuropeptides in the baroreceptor reflex arc: connections between the nucleus of the solitary tract and the ventrolateral medulla oblongata in the rat. Clin Exp Hypertens 17:101–113PubMedCrossRefGoogle Scholar
  5. 5.
    Jacobowitz DM, Kresse A, Skofitsch G (2004) Galanin in the brain: chemoarchitectonics and brain cartography–a historical review. Peptides 25:433–464PubMedCrossRefGoogle Scholar
  6. 6.
    Harfstrand A, Fuxe K, Melander T, Hokfelt T, Agnati LF (1987) Evidence for a cardiovascular role of central galanin neurons: focus on interactions with alpha 2-adrenergic and neuropeptide Y mechanisms. J Cardiovasc Pharmacol 10(Suppl 12):S199–S204PubMedCrossRefGoogle Scholar
  7. 7.
    Hedlund PB, Aguirre JA, Narvaez JA, Fuxe K (1991) Centrally coinjected galanin and a 5-HT1A agonist act synergistically to produce vasodepressor responses in the rat. Eur J Pharmacol 204:87–95PubMedCrossRefGoogle Scholar
  8. 8.
    Narvaez JA, Diaz Z, Aguirre JA, Gonzalez-Baron S, Yanaihara N, Fuxe K et al (1994) Intracisternally injected galanin-(1-15) modulates the cardiovascular responses of galanin-(1-29) and the 5-HT1A receptor agonist 8-OH-DPAT. Eur J Pharmacol 257:257–265PubMedCrossRefGoogle Scholar
  9. 9.
    Branchek T, Smith KE, Walker MW (1998) Molecular biology and pharmacology of galanin receptors. Ann N Y Acad Sci 863:94–107PubMedCrossRefGoogle Scholar
  10. 10.
    O'Donnell D, Ahmad S, Wahlestedt C, Walker P (1999) Expression of the novel galanin receptor subtype GALR2 in the adult rat CNS: distinct distribution from GALR1. J Comp Neurol 409:469–481PubMedCrossRefGoogle Scholar
  11. 11.
    Waters SM, Krause JE (2000) Distribution of galanin-1, -2 and -3 receptor messenger RNAs in central and peripheral rat tissues. Neuroscience 95:265–271PubMedCrossRefGoogle Scholar
  12. 12.
    Smith KE, Walker MW, Artymyshyn R, Bard J, Borowsky B, Tamm JA et al (1998) Cloned human and rat galanin GALR3 receptors. Pharmacology and activation of G-protein inwardly rectifying K + channels. J Biol Chem 273:23321–23326PubMedCrossRefGoogle Scholar
  13. 13.
    Endoh T, Sato D, Wada Y, Shibukawa Y, Ishihara K, Hashimoto S et al (2008) Galanin inhibits calcium channels via Galpha(i)-protein mediated by GalR1 in rat nucleus tractus solitarius. Brain Res 1229:37–46PubMedCrossRefGoogle Scholar
  14. 14.
    Wang S, Hashemi T, Fried S, Clemmons AL, Hawes BE (1998) Differential intracellular signaling of the GalR1 and GalR2 galanin receptor subtypes. Biochemistry 37:6711–6717PubMedCrossRefGoogle Scholar
  15. 15.
    Diaz-Cabiale Z, Cordon MP, Covenas R, Rivera A, Yanaihara N, Fuxe K et al (2002) Propranolol blocks the tachycardia induced by galanin (1-15) but not by galanin (1-29). Regul Pept 107:29–36PubMedCrossRefGoogle Scholar
  16. 16.
    Revington M, Potter EK, McCloskey DI (1990) Prolonged inhibition of cardiac vagal action following sympathetic stimulation and galanin in anaesthetized cats. J Physiol 431:495–503PubMedGoogle Scholar
  17. 17.
    Ulman LG, Potter EK, McCloskey DI (1992) Effects of sympathetic activity and galanin on cardiac vagal action in anaesthetized cats. J Physiol 448:225–235PubMedGoogle Scholar
  18. 18.
    Abbott SB, Pilowsky PM (2009) Galanin microinjection into rostral ventrolateral medulla of the rat is hypotensive and attenuates sympathetic chemoreflex. Am J Physiol Regul Integr Comp Physiol 296:R1019–R1026PubMedCrossRefGoogle Scholar
  19. 19.
    Chen YL, Chan SH, Chan JY (1996) Participation of galanin in baroreflex inhibition of heart rate by hypothalamic PVN in rat. Am J Physiol 271:H1823–H1828PubMedGoogle Scholar
  20. 20.
    Shih CD, Chan SH, Chan JY (1996) Participation of endogenous galanin in the suppression of baroreceptor reflex response by locus coeruleus in the rat. Brain Res 721:76–82PubMedCrossRefGoogle Scholar
  21. 21.
    Diaz-Cabiale Z, Narvaez JA, Marcos P, Cordon MP, Covenas R, Fuxe K et al (1998) Galanin and NH2-terminal galanin fragments in central cardiovascular regulation. Ann N Y Acad Sci 863:421–424PubMedCrossRefGoogle Scholar
  22. 22.
    Hedlund PB, Yanaihara N, Fuxe K (1992) Evidence for specific N-terminal galanin fragment binding sites in the rat brain. Eur J Pharmacol 224:203–205PubMedCrossRefGoogle Scholar
  23. 23.
    Diaz-Cabiale Z, Parrado C, Vela C, Razani H, Covenas R, Fuxe K et al (2005) Role of galanin and galanin(1-15) on central cardiovascular control. Neuropeptides 39:185–190PubMedCrossRefGoogle Scholar
  24. 24.
    Marcos P, Diaz-Cabiale Z, Cordon MP, Covenas R, Yanaihara N, Fuxe K et al (2001) Central galanin and N-terminal galanin fragment induce c-Fos immunoreactivity in the medulla oblongata of the anesthetized rat. Peptides 22:1501–1509PubMedCrossRefGoogle Scholar
  25. 25.
    Narvaez JA, Diaz-Cabiale Z, Hedlund PB, Aguirre JA, Covenas R, Gonzalez-Baron S et al (2000) The galanin receptor antagonist M40 blocks the central cardiovascular actions of the galanin N-terminal fragment (1-15). Eur J Pharmacol 399:197–203PubMedCrossRefGoogle Scholar
  26. 26.
    Fuxe K, Marcellino D, Rivera A, Diaz-Cabiale Z, Filip M, Gago B et al (2008) Receptor-receptor interactions within receptor mosaics. Impact on neuropsychopharmacology. Brain Res Rev 58:415–452PubMedCrossRefGoogle Scholar
  27. 27.
    Diaz-Cabiale Z, Parrado C, Fuxe K, Agnati L, Narvaez JA (2007) Receptor-receptor interactions in central cardiovascular regulation. Focus on neuropeptide/alpha(2)-adrenoreceptor interactions in the nucleus tractus solitarius. J Neural Transm 114:115–125PubMedCrossRefGoogle Scholar
  28. 28.
    Ramage AG, Villalon CM (2008) 5-hydroxytryptamine and cardiovascular regulation. Trends Pharmacol Sci 29:472–481PubMedCrossRefGoogle Scholar
  29. 29.
    Kalia M, Fuxe K, Goldstein M (1985) Rat medulla oblongata. II. Dopaminergic, noradrenergic (A1 and A2) and adrenergic neurons, nerve fibers, and presumptive terminal processes. J Comp Neurol 233:308–332PubMedCrossRefGoogle Scholar
  30. 30.
    Fuxe K (1965) Evidence for the existence of monoamine neurons in the central nervous system. IV. Distribution of monoamine nerve terminals in the central nervous system. Acta Physiol Scand Suppl 247:237Google Scholar
  31. 31.
    Kalia M, Fuxe K, Goldstein M (1985) Rat medulla oblongata. III. Adrenergic (C1 and C2) neurons, nerve fibers and presumptive terminal processes. J Comp Neurol 233:333–349PubMedCrossRefGoogle Scholar
  32. 32.
    Hokfelt T, Fuxe K, Goldstein M, Johansson O (1973) Evidence for adrenaline neurons in the rat brain. Acta Physiol Scand 89:286–288PubMedCrossRefGoogle Scholar
  33. 33.
    Zandberg P, De Jong W, De Wied D (1979) Effect of catecholamine-receptor stimulating agents on blood pressure after local application in the nucleus tractus solitarii of the medulla oblongata. Eur J Pharmacol 55:43–56PubMedCrossRefGoogle Scholar
  34. 34.
    Rockhold RW, Caldwell RW (1980) Cardiovascular effects following clonidine microinjection into the nucleus tractus solitarii of the rat. Neuropharmacology 19:919–922PubMedCrossRefGoogle Scholar
  35. 35.
    Bolme P, Fuxe K (1971) Pharmacological studies on the hypotensive effects of clonidine. Eur J Pharmacol 13:168–174PubMedCrossRefGoogle Scholar
  36. 36.
    Rosin DL, Zeng D, Stornetta RL, Norton FR, Riley T, Okusa MD et al (1993) Immunohistochemical localization of alpha 2A-adrenergic receptors in catecholaminergic and other brainstem neurons in the rat. Neuroscience 56:139–155PubMedCrossRefGoogle Scholar
  37. 37.
    Kobinger W, Pichler L (1980) Relation between central sympathoinhibitory and peripheral pre- and postsynaptic alpha-adrenoceptors as evaluated by different clonidine-like substances in rats. Naunyn Schmiedebergs Arch Pharmacol 315:21–27PubMedCrossRefGoogle Scholar
  38. 38.
    Melander T, Hokfelt T, Rokaeus A, Cuello AC, Oertel WH, Verhofstad A et al (1986) Coexistence of galanin-like immunoreactivity with catecholamines, 5-hydroxytryptamine, GABA and neuropeptides in the rat CNS. J Neurosci 6:3640–3654PubMedGoogle Scholar
  39. 39.
    Diaz-Cabiale Z, Narvaez JA, Yanaihara N, Gonzalez-Baron S, Fuxe K (2000) Galanin/alpha2-receptor interactions in central cardiovascular control. Neuropharmacology 39:1377–1385PubMedCrossRefGoogle Scholar
  40. 40.
    Diaz-Cabiale Z, Narvaez JA, Garcia-Coronel M, Fuxe K (2001) Galanin/alpha2-adrenoceptor interactions in telencephalic and diencephalic regions of the rat. Neuroreport 12:151–155PubMedCrossRefGoogle Scholar
  41. 41.
    Head GA, Mayorov DN (2001) Central angiotensin and baroreceptor control of circulation. Ann N Y Acad Sci 940:361–379PubMedCrossRefGoogle Scholar
  42. 42.
    McKinley MJ, Albiston AL, Allen AM, Mathai ML, May CN, McAllen RM et al (2003) The brain renin-angiotensin system: location and physiological roles. Int J Biochem Cell Biol 35:901–918PubMedCrossRefGoogle Scholar
  43. 43.
    Fior DR, Yang SN, Hedlund PB, Narvaez JA, Agnati LF, Fuxe K (1994) Evidence for an antagonistic angiotensin II/alpha 2-adrenoceptor interaction in the nucleus tractus solitarii. Eur J Pharmacol 262:271–282PubMedCrossRefGoogle Scholar
  44. 44.
    Diz DI, Barnes KL, Ferrario CM (1984) Hypotensive actions of microinjections of angiotensin II into the dorsal motor nucleus of the vagus. J Hypertens Suppl 2:S53–S56PubMedGoogle Scholar
  45. 45.
    Casto R, Phillips MI (1984) A role for central angiotensin in regulation of blood pressure at the nucleus tractus solitarius. Clin Exp Hypertens A 6:1933–1937PubMedCrossRefGoogle Scholar
  46. 46.
    Luoh HF, Chan SH (1998) Participation of AT1 and AT2 receptor subtypes in the tonic inhibitory modulation of baroreceptor reflex response by endogenous angiotensins at the nucleus tractus solitarii in the rat. Brain Res 782:73–82PubMedCrossRefGoogle Scholar
  47. 47.
    Diaz-Cabiale Z, Fuxe K, Covenas R, Gonzalez-Baron S, Narvaez JA (2003) Angiotensin II modulates the cardiovascular responses to microinjection of NPY Y1 and NPY Y2 receptor agonists into the nucleus tractus solitarii of the rat. Brain Res 983:193–200PubMedCrossRefGoogle Scholar
  48. 48.
    Diaz-Cabiale Z, Parrado C, Vela C, Covenas R, Yanaihara N, Fuxe K et al (2005) Intracisternal galanin/angiotensin II interactions in central cardiovascular control. Regul Pept 127:133–140PubMedCrossRefGoogle Scholar
  49. 49.
    Hirase M, Ono K, Yamashita H, Inenaga K (2008) Central injection of galanin inhibits angiotensin II-induced responses in rats. Neuroreport 19:323–326PubMedCrossRefGoogle Scholar
  50. 50.
    Kai A, Ono K, Kawano H, Honda E, Nakanishi O, Inenaga K (2006) Galanin inhibits neural activity in the subfornical organ in rat slice preparation. Neuroscience 143:769–777PubMedCrossRefGoogle Scholar
  51. 51.
    AbdAlla S, Abdel-Baset A, Lother H, el Massiery A, Quitterer U (2005) Mesangial AT1/B2 receptor heterodimers contribute to angiotensin II hyperresponsiveness in experimental hypertension. J Mol Neurosci 26:185–192PubMedCrossRefGoogle Scholar
  52. 52.
    Fior DR, Hedlund PB, Fuxe K (1993) Autoradiographic evidence for a bradykinin/angiotensin II receptor-receptor interaction in the rat brain. Neurosci Lett 163:58–62PubMedCrossRefGoogle Scholar
  53. 53.
    Agnati LF, Ferre S, Lluis C, Franco R, Fuxe K (2003) Molecular mechanisms and therapeutical implications of intramembrane receptor/receptor interactions among heptahelical receptors with examples from the striatopallidal GABA neurons. Pharmacol Rev 55:509–550PubMedCrossRefGoogle Scholar
  54. 54.
    Wirz SA, Davis CN, Lu X, Zal T, Bartfai T (2005) Homodimerization and internalization of galanin type 1 receptor in living CHO cells. Neuropeptides 39:535–546PubMedCrossRefGoogle Scholar
  55. 55.
    Tatemoto K (1982) Neuropeptide Y: complete amino acid sequence of the brain peptide. Proc Natl Acad Sci USA 79:5485–5489PubMedCrossRefGoogle Scholar
  56. 56.
    Lin S, Boey D, Herzog H (2004) NPY and Y receptors: lessons from transgenic and knockout models. Neuropeptides 38:189–200PubMedCrossRefGoogle Scholar
  57. 57.
    Fuxe K, Harfstrand A, Agnati LF, Kalia M, Fredholm B, Svensson T et al (1987) Central catecholamine-neuropeptide Y interactions at the pre- and postsynaptic level in cardiovascular centers. J Cardiovasc Pharmacol 10(Suppl 12):S1–S13PubMedCrossRefGoogle Scholar
  58. 58.
    Yang SN, Fior DR, Hedlund PB, Narvaez JA, Agnati LF, Fuxe K (1994) Coinjections of NPY(1–36) or [Leu31, Pro34]NPY with adrenaline in the nucleus tractus solitarius of the rat counteract the vasodepressor responses to adrenaline. Neurosci Lett 171:27–31PubMedCrossRefGoogle Scholar
  59. 59.
    Barraco RA, Ergene E, Dunbar JC, Ganduri YL, Anderson GF (1991) Y2 receptors for neuropeptide Y in the nucleus of the solitary tract mediate depressor responses. Peptides 12:691–698PubMedCrossRefGoogle Scholar
  60. 60.
    Narvaez JA, Aguirre JA, Fuxe K (1993) Subpicomolar amounts of NPY(13-36) injected into the nucleus tractus solitarius of the rat counteract the cardiovascular responses to L-glutamate. Neurosci Lett 151:182–186PubMedCrossRefGoogle Scholar
  61. 61.
    Diaz-Cabiale Z, Parrado C, Rivera A, de la Calle A, Agnati L, Fuxe K et al (2006) Galanin-neuropeptide Y (NPY) interactions in central cardiovascular control: involvement of the NPY Y receptor subtype. Eur J Neurosci 24:499–508PubMedCrossRefGoogle Scholar
  62. 62.
    Gehlert DR, Schober DA, Morin M, Berglund MM (2007) Co-expression of neuropeptide Y Y1 and Y5 receptors results in heterodimerization and altered functional properties. Biochem Pharmacol 74:1652–1664PubMedCrossRefGoogle Scholar

Copyright information

© Springer Basel AG 2010

Authors and Affiliations

  • Zaida Díaz-Cabiale
    • 1
  • Concepción Parrado
    • 2
  • Manuel Narváez
    • 1
  • Carmelo Millón
    • 1
  • Araceli Puigcerver
    • 3
  • Kjell Fuxe
    • 4
  • José Angel Narváez
    • 1
  1. 1.Department of PhysiologyUniversity of MálagaMálagaSpain
  2. 2.Department of HistologyUniversity of MálagaMálagaSpain
  3. 3.Department of PsychobiologyUniversity of MálagaMálagaSpain
  4. 4.Department of NeuroscienceKarolinska InstitutetStockholmSweden

Personalised recommendations