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Contractile responses to sumatriptan in isolated bovine pulmonary artery rings: relationship to tone and cyclic nucleotide levels.

Abstract：

:We examined responses to the 5-hydroxytryptamine 1D (5-HT1D)-receptor agonist sumatriptan in bovine pulmonary artery rings (2-3 mm ID). The effects of agonist-induced tone and agents that alter intracellular cyclic AMP [cyclic AMP]i or [cyclic GMP]i on responses to sumatriptan were investigated. At resting tension, responses to sumatriptan were slight or not evident. In the presence of tone induced by U46619, responses to sumatriptan (1 nM-30 mM) were greatly potentiated, as were responses to the alpha2-adrenoceptor agonist UK14304. Responses to the alpha 1-adrenoceptor agonist phenylephrine (PE) were potentiated only slightly. In the presence of U46619, addition of the adenylyl cyclase activator, forskolin (1 nM-0.1 microM or isoprenaline (ISO 1 microM) induced relaxations and increases in [cyclic AMP]i and resulted in further potentiation of the contractile response to sumatriptan. Addition of 0.1 microM sodium nitroprusside (SNP) inhibited sumatriptan-induced contractions. Whereas sumatriptan alone did not significantly affect [cyclic AMP]i, in the presence of U46619 it decreased [cyclic AMP]i. This effect of sumatriptan was further enhanced in the presence of forskolin. Sumatriptan increased [cyclic GMP]i. Using a nitric oxide (NO) synthase inhibitor and vessels denuded of endothelium, we showed that the increased [cyclic GMP]i in response to sumatriptan was endothelium-dependent and mediated by NO. This increase in [cyclic GMP]i was not observed in the presence of U46619. By measuring cyclic AMP and cyclic GMP phosphodiesterase (PDE) levels, we demonstrated that the point of "cross-talk" between cyclic nucleotides may not be at the level of total PDE activity. These results highlight the important role of [cyclic AMP], [cyclic GMP]i, and endothelium function in the control of 5-HT1D receptor-mediated vasoconstriction, which is dependent on a decrease in [cyclic AMP]i in the absence of an increase in [cyclic GMP]i.

journal_name

J Cardiovasc Pharmacol

journal_title

Journal of cardiovascular pharmacology

authors

Sweeney G,Templeton A,Clayton RA,Baird M,Sheridan S,Johnston ED,MacLean MR

doi

10.1097/00005344-199511000-00012

subject

Has Abstract

pub_date

1995-11-01 00:00:00

pages

751-60

issue

eissn

0160-2446

issn

1533-4023

journal_volume

pub_type

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Contractile responses to sumatriptan in isolated bovine pulmonary artery rings: relationship to tone and cyclic nucleotide levels.