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.
Marwood
J F
JF
Clinical Pharmacology Department, Royal North Shore Hospital, St. Leonards, New South Wales, Australia.
D000818:Animals; D001158:Arteries / Q000378:metabolism*; D001665:Binding Sites; D004110:Diltiazem / Q000494:pharmacology; D015736:Felodipine; D066298:In Vitro Techniques; D008297:Male; D008345:Manganese / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D009568:Nitrendipine / Q000031:analogs & derivatives / Q000494:pharmacology; D010656:Phenylephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D013623:Tail / Q000098:blood supply; D014700:Verapamil / Q000494:pharmacology
D011942:Receptors, Adrenergic, alpha; D011985:Receptors, Serotonin; D010656:Phenylephrine; D012701:Serotonin; D008345:Manganese; D009568:Nitrendipine; D014700:Verapamil; D004110:Diltiazem; D015736:Felodipine