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Studies on the mechanism of 5‐HT 1 receptor‐induced smooth muscle contraction in dog saphenous vein
Author(s) -
Sumner Michael J.,
Feniuk Wasyl,
McCormick Julie D.,
Humphrey Patrick P. A.
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb09026.x
Subject(s) - medicine , endocrinology , verapamil , agonist , chemistry , contraction (grammar) , muscle contraction , receptor , methoxamine , vascular smooth muscle , calcium , extracellular , voltage dependent calcium channel , biology , biochemistry , smooth muscle
1 We have investigated the mechanism of smooth muscle contraction evoked by activation of 5‐HT 1 ‐like receptors in dog isolated saphenous vein. 2 In the presence of the 5‐HT 2 receptor antagonist, ritanserin (0.1 μ m ), concentration‐effect curves (10 n m ‐300 μ m ) for 5‐hydroxytryptamine (5‐HT)‐induced smooth muscle contraction were biphasic. This could be attributed to a direct action on 5‐HT 1 ‐like receptors at low concentrations of 5‐HT (10 n m ‐10 μ m ) and an indirect (through the release of noradrenaline from sympathetic neurones) activation of postjunctional α‐adrenoceptors at higher 5‐HT concentrations. In contrast, concentration‐effect curves (100 n m –100 μ m ) for sumatriptan‐induced contractions were not biphasic, and were due solely to activation of 5‐HT 1 ‐like receptors. 3 Smooth muscle contractions evoked either by low concentrations of 5‐HT or by sumatriptan were abolished by removal of extracellular calcium and were markedly inhibited, but not abolished, by the calcium channel blocker, verapamil (1–30 μ m ). In contrast, contractions evoked by high concentrations of 5‐HT were markedly less sensitive to removal of extracellular calcium or to verapamil. 4 5‐HT and sumatriptan also inhibited (to a maximum of about 50%) prostaglandin E 2 (PGE 2 ,5 μ m )‐stimulated adenosine 3′:5′‐cyclic monophosphate (cyclic AMP) formation. This effect was mimicked by the α 2 ‐adrenoceptor agonist, azepexole (B‐HT933) but not by the α 1 ‐adrenoceptor agonist, methoxamine. 5 In contrast to mediation of smooth muscle contraction, the 5‐HT 1 ‐like receptor‐mediated inhibition of PGE 2 ‐stimulated cyclic AMP formation evoked by 5‐HT or sumatriptan was not attenuated by removal of extracellular calcium or by verapamil (1 μ m ). 6 A directly‐acting inhibitor of adenylyl cyclase, 2′,3′‐dideoxyadenosine (1 m m ) inhibited PGE 2 ‐stimulated cyclic AMP formation but did not produce smooth muscle contraction. 7 These results suggest that contractile responses of dog isolated saphenous vein arising through activation of 5‐HT 1 ‐like receptors are associated with both an influx of extracellular calcium ions (to a large extent via voltage‐dependent channels) and an inhibition of adenylyl cyclase. However, although these two responses are coupled to the same receptor, they appear to be independent.