Serotonin induces constriction and relaxation of the guinea pig airway

R. A. Baumgartner, Marsha Wills-Karp, M. J. Kaufman, M. Munakata, C. Hirshman

Research output: Contribution to journalArticle

Abstract

The response of guinea pig trachea to 5-hydroxytryptamine (serotonin; 5-HT) was investigated by studying tracheal strips suspended in organ chambers for isometric tension measurements. Serotonin concentrations of 0.1 to 10 μM produced concentration-dependent contractions, whereas at higher concentrations (10-300 μM) the agonist caused concentration-dependent relaxations. The 5-HT2 antagonist ketanserin shifted the bimodal 5-HT response-curve to the right (pA2 for ketanserin was 8.98). The 5-HT(1A) agonist, (+)-8-hydroxy-2-(di-N-propylamino)tetralin hydrobromide and 5-HT3 antagonist, ICS 205930 (3-tropanyl-indole-3-carboxylate) had no effect on the 5-HT-response curve. Incubation with atropine resulted in a depression of the maximal contractility and an increase in the EC50 without changing the bimodal nature of the concentration-response curve. Hexamethonium was able to block the atropine effect without significantly affecting the 5-HT concentration-response curve. Neither the constriction nor the relaxation was altered by propranolol, chlorpheniramine or capsaicin pretreatment. Histamine and carbachol preconstricted airways were also relaxed by 5-HT in a concentration-dependent fashion and this relaxation was antagonized by ketanserin (pKb for ketanserin in histamine preconstricted airways was 9.4). Epithelial denudation did not inhibit the 5-HT-induced relaxation. 5-HT stimulated inositol-monophosphate production which also exhibited a bimodal response and correlated well with the functional response. The above findings suggest that 5-HT causes both constriction and relaxation of the guinea pig airway, and the both responses are antagonized by a 5-HT2 receptor blocker. In addition, part of the constrictor response of 5-HT is mediated through a cholinergic preganglionic pathway. Finally, inositol-monophosphate production induced by 5-HT correlates with the functional response.

Original languageEnglish (US)
Pages (from-to)165-173
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume255
Issue number1
StatePublished - 1990

Fingerprint

Constriction
Serotonin
Guinea Pigs
Ketanserin
tropisetron
Inositol
Atropine
Histamine
Chlorpheniramine
Serotonin 5-HT3 Receptor Antagonists
Serotonin 5-HT2 Receptor Antagonists
Serotonin Receptor Agonists
Hexamethonium
Capsaicin
Carbachol
Trachea
Propranolol
Cholinergic Agents

ASJC Scopus subject areas

  • Pharmacology

Cite this

Baumgartner, R. A., Wills-Karp, M., Kaufman, M. J., Munakata, M., & Hirshman, C. (1990). Serotonin induces constriction and relaxation of the guinea pig airway. Journal of Pharmacology and Experimental Therapeutics, 255(1), 165-173.

Serotonin induces constriction and relaxation of the guinea pig airway. / Baumgartner, R. A.; Wills-Karp, Marsha; Kaufman, M. J.; Munakata, M.; Hirshman, C.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 255, No. 1, 1990, p. 165-173.

Research output: Contribution to journalArticle

Baumgartner, RA, Wills-Karp, M, Kaufman, MJ, Munakata, M & Hirshman, C 1990, 'Serotonin induces constriction and relaxation of the guinea pig airway', Journal of Pharmacology and Experimental Therapeutics, vol. 255, no. 1, pp. 165-173.
Baumgartner, R. A. ; Wills-Karp, Marsha ; Kaufman, M. J. ; Munakata, M. ; Hirshman, C. / Serotonin induces constriction and relaxation of the guinea pig airway. In: Journal of Pharmacology and Experimental Therapeutics. 1990 ; Vol. 255, No. 1. pp. 165-173.
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