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Edvinsson L, Hardebo JE, Owman C.
“Pharmacological Analysis of 5-Hydroxytryptamine Receptors in Isolated Intracranial and Extracranial Vessels of Cat and Man”.
Circulation Res.. 1978;42(I):143-51.
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Abstract
A pharmacological analysis of 5-hydroxytryptamine receptors in isolated intracranial and extracranial vessels of cat and man is reported. In intra- and extracranial arteries from cat and man (under conditions in which dilation was blocked), 5-hydroxytryptamine (5-HT, Sigma-Chem.) and D-lysergic acid diethylamide (LSD, Sandoz) produced contraction at lower doses than that produced by tryptamine. Methysergide inhibited the 5-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 curve. Increasing concentrations of phenoxybenzamine (Dibenzyline; SK+F) from 3 x 10-8M to 3 x 10-6M caused graded blockade of the 5-HT effect with a decrease in maximum and slope of the dose-response cruves for intracranial and extracranial vessels. Dose-response curves obtained with 5-HT were not influenced by phentolamine (CIBA-Geigy) until relatively high antagonist concentrations (3 x 10 6M) had been reached. The contractile effects of 5-HT on both types of arteries appeared to be mediated by 5-HT receptors, but the receptors had different characteristics in the sense that the mode of antagonism by methysergide was different. The dissociation constant (KB) end the corresponding pA2 value (8.61 x 10-,M and 8.21, reapectively) for the interaction between methysergide and 5-HT in extracranial arteries conformed with that reported for other smooth muscle tissues. The dilator response was studied in arteries given an active tonic contraction with prostaglandin F2a (Astra). Both 5-HT and tryptamine produced a dose-dependent dilation, 5-HT being the more potent. Neither methysergide nor LSD antagonized the response ina competitive manner, whereas propranolol (Inderal, Scanmeda) and l-N-isopropyl-p-nitrophen ethanolamine (INPEA, Selvi) caused a parael shift of the log dose-response curves (tested for 5-HT). The mean values for KB (pA2) in the presence of propranolol were 1.93 x 10-8M (8.29) for the intracranial and 1.83 x 10-8M (8.50) for the extracranial vessels. Calculated pA2 values with INPEA were 8.47 and 7.93, respectively. The mode of inhibition by the 8-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 p-receptor.
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