Abstract
5-Hydroxytryptamine (5-HT)-receptor subtypes on pig basilar arteries were investigated by measuring the contractile responses to 5-HT agonists, the effects of antagonists on the responses and by carrying out a radioligand binding assay with [3H]5-HT. The rank order of contractile agonist potency (according to the pEC50 values) was 5-carboxamidotryptamine > or = 5-HT > alpha-methyl-5-HT > (+/-)-8-hydroxy-dipropylaminotetralin. The contractile responses were not affected by endothelial denudation, and the 5-HT-induced contractions were antagonized competitively by ketanserin. Methiothepin shifted the 5-HT concentration-response curves to the right and downwards in a concentration-dependent manner. In the presence of ketanserin (10(-6) M), however, methiothepin antagonized the 5-HT-induced contractions competitively. Specific [3H]5-HT binding to 5-HT receptors was saturable, reversible and showed high (Kd, 2.5 nM) and low (Kd, 710 nM) affinities, with respective Bmax values of 29.5 and 1950 fmol/mg protein. These results indicate that both 5-HT1 and 5-HT2 receptors are present on pig basilar arterial smooth muscle cells, and their stimulation results in contraction.
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