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In intra- and extracranial arteries from cat and man (under conditions in which dilation was blocked), 5-hydroxytryptamine (5-HT) and D-lysergic acid diethylamide (LSD) produced a contraction at lower doses than that produced by tryptamine. Methysergide inhibited the S-HT-induced contraction of the extracranial arteries in a competitive manner. In intracranial arteries the inhibition comprised a reduction in slope and maximum of the log dose-response curves. The contractile effects of 5-HT on both types of arteries appear to be mediated by 5-HT receptors, but the receptors have different characteristics in the sense that the mode of antagonism by methysergide was different. The dissociation constant (Kg) and the corresponding pA2 value (8.61 x 10 " M and 8.21, respectively) for the interaction between methysergide and 5-HT in extracranial arteries conform with that reported for other smooth muscle tissues. The dilator response was tested in arteries given an active tonic contraction with prostaglandin F2(1. Both 5-HT and tryptamine produced a dose-dependent dilation, 5-HT being the more potent. Neither methysergide nor LSD antagonized the response in a competitve manner whereas the two /3- receptor antagonists, propranolol and 1-JV-isopropyl-p-nitrophenyl-ethanolamine (INPEA), caused a parallel shift of the log dose-response curves (tested for 5-HT). The mean values for Kg (pA2) in the presence of propranolol were 1.93 x 10* M (8.29) for the intracranial and 1.83 x 10* M (8.50) for the extracranial vessels. Calculated pA, values with INPEA were 8.47 and 7.93, respectively. The mode of inhibition by the β-antagonists suggests that the dilator effect of 5-HT is mediated by a receptor that may be the same as, or closely related to, the adrenergic fireceptor.

Pharmacological analysis of 5-hydroxytryptamine receptors in isolated intracranial and extracranial vessels of cat and man.