5-Hydroxytryptamine and related drugs and transmitter release from autonomic nerves in the cardiovascular system

  • M. Göthert
  • K. Fink
  • G. Molderings
  • E. Schlicker
Part of the Developments in CardioCardiovascular Pharmacology of 5-Hydroxytryptamine book series (DICM, volume 106)


Under in vivo conditions, 5-hydroxytryptamine (5-HT) and related drugs influence transmitter release from autonomic nerves in the cardiovascular system not only by acting on the sympathetic and parasympathetic nerve endings, but also by modifying ganglionic transmission [1] as well as central regulation of circulatory function [2, 3]. Within this framework, the present report will focus on effects of relevant drugs on the peripheral autonomic nerve endings, particularly those innervating cardiovascular tissues.


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  1. 1.
    Fozard JR (1984): Neuronal 5-HT receptors in the periphery. Neuropharmacology 23 : 1473 – 1486.PubMedCrossRefGoogle Scholar
  2. 2.
    Kuhn DM, Wolf WA, Lovenberg W (1980): Review of the role of the central serotonergic neuronal system in blood pressure regulation. Hypertension 2: 243 – 255.PubMedCrossRefGoogle Scholar
  3. 3.
    Wolf WA, Kuhn DM, Lovenberg W (1981): Pressor effects of dorsal raphe stimulation and intrahypothalamic application of serotonin in the spontaneously hypertensive rat. Brain Res 208: 192 – 197.PubMedCrossRefGoogle Scholar
  4. 4.
    McGrath MA (1977): 5-Hydroxytryptamine and neurotransmitter release in canine blood vessels. Inhibition by low and augmentation by high concentrations. Circ Res 41: 428–435.PubMedCrossRefGoogle Scholar
  5. 5.
    Humphrey PPA (1978). The effects of a-adrenoceptor antagonists on contractile responses to 5-hydroxytryptamine in dog saphenous vein. Br J Pharmacol 63: 671 – 675.PubMedCrossRefGoogle Scholar
  6. 6.
    Marin J, Arias M, Salaices M. Sanchez CF, Recio LM (1981): Vasoconstrictor effects of serotonin in the isolated superior mesenteric artery of cat. Gen Pharmacol 12: 97–101.PubMedCrossRefGoogle Scholar
  7. 7.
    Freeman WK, Rorie DK, Tyce GM (1981): Effects of 5-hydroxytryptamine on neuroef- fector junction in human pulmonary artery. J appl Physiol Respir Environ 51: 693 – 698.Google Scholar
  8. 8.
    Göthert M, Schlicker E, Kollecker P (1986): Receptor mediated effects of serotonin and 5-methoxytryptamine on noradrenaline release in the rat vena cava and in the heart of the pithed rat. Naunyn-Schmiedeberg’s Arch Pharmacol 332: 124 – 130.CrossRefGoogle Scholar
  9. 9.
    . Göthert M, Dührsen U (1979): Effects of 5-hydroxytryptamine and related compounds on the sympathetic nerves of the rabbit heart. Naunyn-Schmiedeberg’s Arch Pharmacol 308: 9 – 18.CrossRefGoogle Scholar
  10. 10.
    Trendelenburg U (1960): The action of histamine and 5-hydroxytryptamine on isolated mammalian atria. J Pharmacol exp Ther 130: 450 – 460.PubMedGoogle Scholar
  11. 11.
    Jacob J, Poite-Bevierre M (1960): Actions de la serotonine et de la benzyl-l-demethyl- 2,5-serotonine sur le coeur isole de lapin. Arch int Pharmacodyn Ther 127: 11 – 26.PubMedGoogle Scholar
  12. 12.
    Fozard JR, Mwaluko GMP (1976): Mechanism of the indirect sympathomimetic effect of 5-hydroxytryptamine on the isolated heart of the rabbit. Br J Pharmacol 57: 115 – 125.PubMedCrossRefGoogle Scholar
  13. 13.
    Fozard JR, Mobarok Ali ATM (1978): Receptors for 5-hydroxytryptamine on the sympathetic nerves of the rabbit heart. Naunyn-Schmiedeberg’s Arch Pharmacol 301: 223 – 235.CrossRefGoogle Scholar
  14. 14.
    Göthert M, Klupp N (1978): Cardiovascular effects of neurotoxic indolethylamines. Ann N YAcadSci 305: 457 – 476.CrossRefGoogle Scholar
  15. 15.
    Engel G, Göthert M, Hoyer D, Schlicker E, Hillenbrand K (1986): Identity of inhibitory presynaptic 5-hydroxytryptamine (5-HT) autoreceptors in the rat brain cortex with 5-HT1B binding sites. Naunyn-Schmiedeberg’s Arch Pharmacol 332: 1 – 7.CrossRefGoogle Scholar
  16. 16.
    Kilpatrick GJ, Jones BJ, Tyers MB (1987): Identification and distribution of 5-HT3 receptors in brain using radioligand binding. Nature 330: 746 – 748.PubMedCrossRefGoogle Scholar
  17. 17.
    Neijt HC, Karpf A, Schoeffter P, Engel G, Hoyer D (1988): Characterisation of 5-HT3 recognition sites in membranes of NG 108–15 neuroblastoma-glioma cells with [3H]ICS 205–930. Naunyn-Schmiedeberg’s Arch Pharmacol 337: 493 – 499.CrossRefGoogle Scholar
  18. 18.
    Richardson BP, Engel G, Donatsch P, Stadler PA (1985): Identification of serotonin M-receptor subtypes and their specific blockade by a new class of drugs. Nature 316: 126 – 131.PubMedCrossRefGoogle Scholar
  19. 19.
    Göthert M, Dührsen U, Rieckesmann J-M (1979): Ethanol, anaesthetics and other lipophilic drugs preferentially inhibit 5-hydroxytryptamine- and acetylcholine-induced noradrenaline release from sympathetic nerves. Arch int Pharmacodyn Ther 242: 196–209.PubMedGoogle Scholar
  20. 20.
    Fozard JR, Mobarok Ali ATM (1978): Blockade of neuronal tryptamine receptors by metoclopramide. European J Pharmacol 49: 109 – 112.CrossRefGoogle Scholar
  21. 21.
    Fozard JR, Mobarok Ali ATM, Newgrosh G (1979): Blockade of serotonin receptors on autonomic neurones by (–)-cocaine and some related compounds. European J Pharmacol 59: 195 – 210.CrossRefGoogle Scholar
  22. 22.
    Fozard JR (1984): MDL 72222: a potent and highly selective antagonist at neuronal 5-hydroxytryptamine receptors. Naunyn-Schmiedeberg’s Arch Pharmacol 326: 36 – 44.CrossRefGoogle Scholar
  23. 23.
    Bradley PB, Engel G, Feniuk W, Fozard JR, Humphrey PPA, Middlemiss DN, Mylecharane EJ, Richardson BP, Saxena PR (1986): Proposals for the classification and nomenclature of functional receptors for 5-hydroxytryptamine. Neuropharmacology 25: 563 – 576.PubMedCrossRefGoogle Scholar
  24. 24.
    Leff P, Martin G (1988): The classification of 5-hydroxytryptamine receptors. Medicinal Research Reviews 8: 187–202.PubMedCrossRefGoogle Scholar
  25. 25.
    Peroutka SJ (1988): 5-Hydroxytryptamine receptor subtypes. Ann Rev Neurosci 11: 45–60.PubMedCrossRefGoogle Scholar
  26. 26.
    Feniuk W, Humphrey PPA, Watts AD (1979): Presynaptic inhibitory action of 5-hydroxytryptamine in dog isolated saphenous vein. Br J Pharmacol 67: 247 – 254.PubMedCrossRefGoogle Scholar
  27. 27.
    Watts AD, Feniuk W, Humphrey PPA (1981): A prejunctional action of 5-hydroxytryptamine and methysergide on noradrenergic nerves in dog isolated saphenous vein. J Pharm Pharmacol 33: 515 – 520.PubMedCrossRefGoogle Scholar
  28. 28.
    Engel G, Gothert M, Muller-Schweinitzer E, Schlicker E, Sistonen L, Stadler PA (1983): Evidence for common pharmacological properties of [3H]5-hydroxytryptamine binding sites, presynaptic 5-hydroxytryptamine autoreceptors in CNS and inhibitory presynaptic 5-hydroxytryptamine receptors on sympathetic nerves. Naunyn-Schmiedeberg’s Arch Pharmacol 324: 116 – 124.CrossRefGoogle Scholar
  29. 29.
    Lorenz RR, Vanhoutte PM (1985): Prejunctional adrenergic inhibition by aggregating platelets in canine blood vessels. Am J Physiol 249: H685 – H689.Google Scholar
  30. 30.
    Cohen RA (1985): Serotonergic prejunctional inhibition of canine coronary adrenergic nerves. J Pharmacol Exp Ther 235: 76 – 80.PubMedGoogle Scholar
  31. 31.
    Cohen RA (1987): Inhibition of adrenergic neurotransmission in canine tibial artery after exposure to 5-hydroxytryptamine in vitro. J Pharmacol Exp Ther 242: 493 – 499.PubMedGoogle Scholar
  32. 32.
    Charlton KG, Bond RA, Clarke DE (1986): An inhibitory prejunctional 5-HT1-like receptor in the isolated perfused rat kidney. Apparent distinction from the 5-HT1A, 5-HT1B and 5-HT1c subtypes. Naunyn-Schmiedeberg’s Arch Pharmacol 332: 8 – 15.CrossRefGoogle Scholar
  33. 33.
    Göthert M, Kollecker P, Rohm N, Zerkowski HR (1986): Inhibitory presynaptic 5-hydroxytryptamine (5-HT) receptors on the sympathetic nerves of the human saphenous vein. Naunyn-Schmiedeberg’s Arch Pharmacol 332: 317 – 323.CrossRefGoogle Scholar
  34. 34.
    Schlicker E, Göthert M (1987): Noradrenaline release and its modulation via presynaptic serotonin receptors in blood vessels of spontaneously hypertensive rats. J Cardiovasc Pharmacol 10 (Suppl. 4): 141 – 143.Google Scholar
  35. 35.
    Molderings GJ, Fink K, Schlicker E, Göthert M (1987): Inhibition of noradrenaline release via presynaptic 5-HT1B receptors of the rat vena cava. Naunyn-Schmiedeberg’s Arch Pharmacol 336: 245 – 250.Google Scholar
  36. 36.
    Docherty JR (1988): Investigations of cardiovascular 5-hydroxytryptamine receptor subtypes in the rat. Naunyn-Schmiedeberg’s Arch Pharmacol 337: 1 – 8.CrossRefGoogle Scholar
  37. 37.
    Adler-Graschinsky E (1983): Dual presynaptic effects of 5-hydroxytryptamine on peripheral noradrenergic synapses. JAuton Pharmacol 3: 303 – 315.Google Scholar
  38. 38.
    Adler-Graschinsky E, Butta NV, Elgoyhen AB (1986): Serotonin uptake inhibitors and the prejunctional effects of serotonin on peripheral sympathetic nerves. Life Sciences 39: 61 - 68.PubMedCrossRefGoogle Scholar
  39. 39.
    Phillips CA, Mylecharane EJ, Shaw J (1985): Mechanisms involved in the vasodilator action of 5-hydroxytryptamine in the dog femoral arterial circulation in vivo. European J Pharmacol 113: 325 – 334.CrossRefGoogle Scholar
  40. 40.
    Martinez AA, Lokhandwala MF (1980): Evidence for a presynaptic inhibitory action of 5-hydroxytryptamine on sympathetic neurotransmission to the myocardium. European J Pharmacol 63: 303 – 311.CrossRefGoogle Scholar
  41. 41.
    Kimura T, Satoh S (1983): Presynaptic inhibition by serotonin of cardiac sympathetic transmission in dogs. Clin Exp Pharmacol Physiol 10: 535 – 542.PubMedCrossRefGoogle Scholar
  42. 42.
    Molderings GJ, Göthert M, Fink K, Roth E, Schlicker E (1989): Inhibition of noradrenaline release in the pig coronary artery via a novel serotonin receptor. Eur J Pharmacol 164: 213–222.PubMedCrossRefGoogle Scholar
  43. 43.
    Bom AH, Duncker DJ, Saxena PR, Verdouw PD (1988): 5-Hydroxytryptamine-induced tachycardia in the pig: possible involvement of a new type of 5-HT receptor. Br J Pharmacol 93:663–671.PubMedCrossRefGoogle Scholar
  44. 44.
    Verbeuren TJ, Jordaens FH, Herman AG (1983): Accumulation and release of [3H]-5- hydroxytryptamine in saphenous veins and cerebral arteries of the dog. J Pharmacol Exp Ther 226: 579–588.PubMedGoogle Scholar
  45. 45.
    Saito A, Lee TJ-F (1987): Serotonin as an alternative transmitter in sympathetic nerves of large cerebral arteries of the rabbit. Circ Res 60: 220–228.PubMedCrossRefGoogle Scholar
  46. 46.
    Kilbinger H, Pfeuffer-Friedrich I (1985): Two types of receptors for 5-hydroxytryptamine on the cholinergic nerves of the guinea-pig myenteric plexus. Br J Pharmacol 85: 529–539.PubMedCrossRefGoogle Scholar
  47. 47.
    Fozard JR, Kilbinger H (1985): 8-OH-DPAT inhibits transmitter release from guinea-pig enteric cholinergic neurones by activating 5-HT1A receptors. Br J Pharmacol 86, 601 P.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 1990

Authors and Affiliations

  • M. Göthert
  • K. Fink
  • G. Molderings
  • E. Schlicker

There are no affiliations available

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