EFFECTS OF 5HT(2) RECEPTOR ANTAGONISTS ON RESPONSES TO POTASSIUM DEPOLARIZATION IN RAT ISOLATED AORTA

1. In order to determine whether 5HT(2) receptor antagonists can modif y Ca2+ uptake via voltage-operated Ca2+ channel (VOC) in arterial smoo th muscle, a comparative study of the effects of selected Ca2+ uptake blockers and 5HT(2) receptor antagonists on K+-induced contractions of rat aortic strip was undertaken. 2. The antagonist drugs studied incl uded the Ca2+ uptake blockers verapamil, nifedipine, felodipine, dilti azem and cinnarizine, the 5HT(2) receptor antagonists cyproheptadine, ritanserin, mianserin, and ketanserin and the alpha(1)-adrenoceptor an tagonist prazosin. 3. With the notable exception of prazosin, each of these compounds diminished K+-induced aortic responses. 4. The followi ng order of potencies (mean IC50 values in mol/L) was established: fel odipine (7.0 x 10(-11)) >nifedipine (4.8 x 10(-9)) >verapamil (5.5 x 1 0(-8)) >cyproheptadine (6.2 x 10(-8)) >diltiazem (4.1 x 10(-7)) >cinna rizine (1.3 x 10(-6)) >ritanserin (1.8 x 10(-6)) >ketanserin (9.0 x 10 (-6)) >mianserin (2.0 x 10(-5)). 5. The results suggest that antagonis ts of 5HT(2) receptors can modulate Ca2+ uptake via VOC in rat aorta.