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. 1993 Feb;108(2):431–435. doi: 10.1111/j.1476-5381.1993.tb12821.x

Effects of capsaicin and 5-HT3 antagonists on 5-hydroxytryptamine-evoked release of calcitonin gene-related peptide in the guinea-pig heart.

M Tramontana 1, S Giuliani 1, E Del Bianco 1, A Lecci 1, C A Maggi 1, S Evangelista 1, P Geppetti 1
PMCID: PMC1907963  PMID: 8448594

Abstract

1. The effect of 5-hydroxytryptamine (5-HT) on the release of calcitonin gene-related peptide (CGRP) was studied directly in the isolated perfused heart and indirectly in the isolated left atria of guinea-pig. 2. 5-HT injection into the guinea-pig isolated and perfused heart evoked a dose-dependent (1-100 microM) release of CGRP-like immunoreactivity (LI) that was abolished by in vitro pretreatment with capsaicin and was not affected by indomethacin. 3. Chlorophenyldiguanide (CPD, 100 microM), but not 8-hydroxy-dipropylaminotetralin (8-OH-DPAT, 100 microM), sumatriptan (100 microM) or 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI, 100 microM) evoked a release of CGRP-LI. Ondansetron (10 microM) or ICS205-930 (20 microM) completely abolished the 5-HT (100 microM)-evoked CGRP-LI release. 4. In the isolated electrically driven left atria of the guinea-pig 5-HT (1-10 microM) and CPD (3-100 microM) produced a positive inotropic response, which was abolished by capsaicin pretreatment. 8-OH-DPAT (10 microM) and DOI (10 microM) were inactive. Ondansetron inhibited the response to 5-HT with a pA2 of 6.50 (CL 6.08-6.91). 5. It is concluded that 5-HT causes a release of CGRP in the whole heart and a positive inotropic response in the isolated atria of guinea-pig. Both these effects are sensitive to capsaicin pretreatment and to 5-HT3 antagonists.

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Selected References

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  1. ARUNLAKSHANA O., SCHILD H. O. Some quantitative uses of drug antagonists. Br J Pharmacol Chemother. 1959 Mar;14(1):48–58. doi: 10.1111/j.1476-5381.1959.tb00928.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baxter G. S., Craig D. A., Clarke D. E. 5-Hydroxytryptamine4 receptors mediate relaxation of the rat oesophageal tunica muscularis mucosae. Naunyn Schmiedebergs Arch Pharmacol. 1991 May;343(5):439–446. doi: 10.1007/BF00169544. [DOI] [PubMed] [Google Scholar]
  3. Bernoussi A., Rioux F. Effects of capsaicin desensitization on the stimulatory effect of kinins, prostaglandins, biogenic amines and various drugs in guinea-pig isolated atria. Br J Pharmacol. 1989 Mar;96(3):563–572. doi: 10.1111/j.1476-5381.1989.tb11854.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bradley P. B., Engel G., Feniuk W., Fozard J. R., Humphrey P. P., Middlemiss D. N., Mylecharane E. J., Richardson B. P., Saxena P. R. Proposals for the classification and nomenclature of functional receptors for 5-hydroxytryptamine. Neuropharmacology. 1986 Jun;25(6):563–576. doi: 10.1016/0028-3908(86)90207-8. [DOI] [PubMed] [Google Scholar]
  5. Butler A., Elswood C. J., Burridge J., Ireland S. J., Bunce K. T., Kilpatrick G. J., Tyers M. B. The pharmacological characterization of 5-HT3 receptors in three isolated preparations derived from guinea-pig tissues. Br J Pharmacol. 1990 Nov;101(3):591–598. doi: 10.1111/j.1476-5381.1990.tb14126.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Butler A., Hill J. M., Ireland S. J., Jordan C. C., Tyers M. B. Pharmacological properties of GR38032F, a novel antagonist at 5-HT3 receptors. Br J Pharmacol. 1988 Jun;94(2):397–412. doi: 10.1111/j.1476-5381.1988.tb11542.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fozard J. R., Ali A. T. Receptors for 5-hydroxytryptamine on the sympathetic nerves of the rabbit heart. Naunyn Schmiedebergs Arch Pharmacol. 1978 Jan-Feb;301(3):223–235. doi: 10.1007/BF00507041. [DOI] [PubMed] [Google Scholar]
  8. Franco-Cereceda A., Lundberg J. M. Calcitonin gene-related peptide (CGRP) and capsaicin-induced stimulation of heart contractile rate and force. Naunyn Schmiedebergs Arch Pharmacol. 1985 Nov;331(2-3):146–151. doi: 10.1007/BF00634231. [DOI] [PubMed] [Google Scholar]
  9. Geppetti P., Del Bianco E., Tramontana M., Vigano T., Folco G. C., Maggi C. A., Manzini S., Fanciullacci M. Arachidonic acid and bradykinin share a common pathway to release neuropeptide from capsaicin-sensitive sensory nerve fibers of the guinea pig heart. J Pharmacol Exp Ther. 1991 Nov;259(2):759–765. [PubMed] [Google Scholar]
  10. Geppetti P., Frilli S., Renzi D., Santicioli P., Maggi C. A., Theodorsson E., Fanciullacci M. Distribution of calcitonin gene-related peptide-like immunoreactivity in various rat tissues: correlation with substance P and other tachykinins and sensitivity to capsaicin. Regul Pept. 1988 Dec;23(3):289–298. doi: 10.1016/0167-0115(88)90229-7. [DOI] [PubMed] [Google Scholar]
  11. Geppetti P., Maggi C. A., Perretti F., Frilli S., Manzini S. Simultaneous release by bradykinin of substance P- and calcitonin gene-related peptide immunoreactivities from capsaicin-sensitive structures in guinea-pig heart. Br J Pharmacol. 1988 Jun;94(2):288–290. doi: 10.1111/j.1476-5381.1988.tb11528.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Geppetti P., Tramontana M., Santicioli P., Del Bianco E., Giuliani S., Maggi C. A. Bradykinin-induced release of calcitonin gene-related peptide from capsaicin-sensitive nerves in guinea-pig atria: mechanism of action and calcium requirements. Neuroscience. 1990;38(3):687–692. doi: 10.1016/0306-4522(90)90062-9. [DOI] [PubMed] [Google Scholar]
  13. Giordano J., Rogers L. V. Peripherally administered serotonin 5-HT3 receptor antagonists reduce inflammatory pain in rats. Eur J Pharmacol. 1989 Oct 24;170(1-2):83–86. doi: 10.1016/0014-2999(89)90137-4. [DOI] [PubMed] [Google Scholar]
  14. Giuliani S., Maggi C. A., Meli A. Prejunctional modulatory action of neuropeptide Y on peripheral terminals of capsaicin-sensitive sensory nerves. Br J Pharmacol. 1989 Oct;98(2):407–412. doi: 10.1111/j.1476-5381.1989.tb12611.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Holzer P. Capsaicin: cellular targets, mechanisms of action, and selectivity for thin sensory neurons. Pharmacol Rev. 1991 Jun;43(2):143–201. [PubMed] [Google Scholar]
  16. Hoyer D. Serotonin 5-HT3, 5-HT4, and 5-HT-M receptors. Neuropsychopharmacology. 1990 Oct-Dec;3(5-6):371–383. [PubMed] [Google Scholar]
  17. Jancsó G., Kiraly E., Jancsó-Gábor A. Pharmacologically induced selective degeneration of chemosensitive primary sensory neurones. Nature. 1977 Dec 22;270(5639):741–743. doi: 10.1038/270741a0. [DOI] [PubMed] [Google Scholar]
  18. Kaumann A. J., Sanders L., Brown A. M., Murray K. J., Brown M. J. A 5-hydroxytryptamine receptor in human atrium. Br J Pharmacol. 1990 Aug;100(4):879–885. doi: 10.1111/j.1476-5381.1990.tb14108.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Maggi C. A. The pharmacology of the efferent function of sensory nerves. J Auton Pharmacol. 1991 Jun;11(3):173–208. doi: 10.1111/j.1474-8673.1991.tb00317.x. [DOI] [PubMed] [Google Scholar]
  20. Manzini S., Perretti F., De Benedetti L., Pradelles P., Maggi C. A., Geppetti P. A comparison of bradykinin- and capsaicin-induced myocardial and coronary effects in isolated perfused heart of guinea-pig: involvement of substance P and calcitonin gene-related peptide release. Br J Pharmacol. 1989 Jun;97(2):303–312. doi: 10.1111/j.1476-5381.1989.tb11955.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Mapp C. E., Boniotti A., Graf P. D., Chitano P., Fabbri L. M., Nadel J. A. Bronchial smooth muscle responses evoked by toluene diisocyanate are inhibited by ruthenium red and by indomethacin. Eur J Pharmacol. 1991 Jul 23;200(1):73–76. doi: 10.1016/0014-2999(91)90667-f. [DOI] [PubMed] [Google Scholar]
  22. Richardson B. P., Engel G., Donatsch P., Stadler P. A. Identification of serotonin M-receptor subtypes and their specific blockade by a new class of drugs. Nature. 1985 Jul 11;316(6024):126–131. doi: 10.1038/316126a0. [DOI] [PubMed] [Google Scholar]
  23. Robertson B., Bevan S. Properties of 5-hydroxytryptamine3 receptor-gated currents in adult rat dorsal root ganglion neurones. Br J Pharmacol. 1991 Jan;102(1):272–276. doi: 10.1111/j.1476-5381.1991.tb12165.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Saito A., Kimura S., Goto K. Calcitonin gene-related peptide as potential neurotransmitter in guinea pig right atrium. Am J Physiol. 1986 Apr;250(4 Pt 2):H693–H698. doi: 10.1152/ajpheart.1986.250.4.H693. [DOI] [PubMed] [Google Scholar]
  25. Saria A., Martling C. R., Yan Z., Theodorsson-Norheim E., Gamse R., Lundberg J. M. Release of multiple tachykinins from capsaicin-sensitive sensory nerves in the lung by bradykinin, histamine, dimethylphenyl piperazinium, and vagal nerve stimulation. Am Rev Respir Dis. 1988 Jun;137(6):1330–1335. doi: 10.1164/ajrccm/137.6.1330. [DOI] [PubMed] [Google Scholar]
  26. Sigrist S., Franco-Cereceda A., Muff R., Henke H., Lundberg J. M., Fischer J. A. Specific receptor and cardiovascular effects of calcitonin gene-related peptide. Endocrinology. 1986 Jul;119(1):381–389. doi: 10.1210/endo-119-1-381. [DOI] [PubMed] [Google Scholar]
  27. Thorén P. Role of cardiac vagal C-fibers in cardiovascular control. Rev Physiol Biochem Pharmacol. 1979;86:1–94. doi: 10.1007/BFb0031531. [DOI] [PubMed] [Google Scholar]
  28. Vedder H., Otten U. Biosynthesis and release of tachykinins from rat sensory neurons in culture. J Neurosci Res. 1991 Oct;30(2):288–299. doi: 10.1002/jnr.490300203. [DOI] [PubMed] [Google Scholar]

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