Agonist-induced desensitization of 5-HT(2) receptors on cultured calf aortic smooth muscle cells.
[(32)P]Phosphatidic acid (PA)-formation was quantified in calf aortic smooth muscle cultures for measuring the activation of the signal transducing system coupled to the 5-hydroxytryptamine(2)-(5-HT(2)) receptor. [(32)P]PA-formation was increased upon stimulation of smooth muscle cells with serotonin (5-HT) and 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM), but not with the 5-HT(1) agonists N,N-dipropyl-8-hydroxy-2-aminotetralin and RU 24969. The potency of drugs to inhibit the 5-HT induced [(32)P]PA-formation closely corresponded to their binding affinity for 5-HT(2) receptors. 24-Hour treatment of smooth muscle cultures with 5-HT or DOM resulted in a substantial decrease of 5-HT induced [(32)P]PA-formation. In contrast to the anomalous 5-HT(2) receptor regulation in vivo, 5-HT(2) receptors on smooth muscle cells appeared to be desensitized by agonist treatment.
Pauwels
P J
PJ
Department of Biochemical Pharmacology, Janssen Research Foundation, B-2340 Beerse, Belgium.
Van Gompel
P
P
de Chaffoy de Courcelles
D
D
Leysen
J E
JE