Studies on the site of the interaction between alpha 1-adrenoceptors and 5-HT2 receptors in rat tail arteries

Isolated perfused rat tail arteries were used to examine the hypothesis that alpha 1-adrenoceptors and 5-HT2 receptors overlap on the vascular smooth muscle membrane. The effects of a series of Ca2+ uptake blockers on responses to 5-hydroxytryptamine (5-HT) and phenylephrine (PE) were determined. Mn2+ ion, which inhibits Ca2+ entry to cells, reduced the maximal responses to 5-HT and PE to 19% +/- 10% and 78% +/- 6%, respectively, of the control maximum response. Thus, the constrictor action of these two amines appeared to depend, to markedly different extents, upon stimulation of Ca2+ uptake. The Ca2+ uptake blockers felodipine, diltiazem, and verapamil, in concentrations ranging from 10(-8) to 10(-5) M, all lowered the maximal arterial responses to 5-HT and PE by 25-37% and 27-35%, respectively, of the control maxima. This was consistent with noncompetitive antagonism of 5-HT2 receptors and alpha 1-adrenoceptors, and suggests an action of Ca2+ channels. In addition, verapamil shifted the dose-response curves for both 5-HT and PE to the right in parallel, indicative of competitive antagonism. It is suggested that 5-HT2 receptors and alpha 1-adrenoceptors are located at or near Ca2+ channels, and the point at which they overlap may be the verapamil binding site.