Effects of 5HT2 receptor antagonists on responses to potassium depolarization in rat isolated aorta.
1. In order to determine whether 5HT2 receptor antagonists can modify Ca2+ uptake via voltage-operated Ca2+ channel (VOC) in arterial smooth muscle, a comparative study of the effects of selected Ca2+ uptake blockers and 5HT2 receptor antagonists on K(+)-induced contractions of rat aortic strip was undertaken. 2. The antagonist drugs studied included the Ca2+ uptake blockers verapamil, nifedipine, felodipine, diltiazem and cinnarizine, the 5HT2 receptor antagonists cyproheptadine, ritanserin, mianserin, and ketanserin and the alpha 1-adrenoceptor antagonist prazosin. 3. With the notable exception of prazosin, each of these compounds diminished K(+)-induced aortic responses. 4. The following order of potencies (mean IC50 values in mol/L) was established: felodipine (7.0 x 10(-11)) > nifedipine (4.8 x 10(-9) > verapamil (5.5 x 10(-8)) > cyproheptadine (6.2 x 10(-8)) > diltiazem (4.1 x 10(-7)) > cinnarizine (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 antagonists of 5HT2 receptors can modulate Ca2+ uptake via VOC in rat aorta.
Okoro
E O
EO
Department of Clinical Pharmacology, Royal North Shore Hospital, St Leonards, New South Wales, Australia.
Marwood
J F
JF
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D002936:Cinnarizine / Q000494:pharmacology; D003533:Cyproheptadine / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D004357:Drug Synergism; D015736:Felodipine / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008803:Mianserin / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D011188:Potassium / Q000737:chemistry / Q000502:physiology*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D015203:Reproducibility of Results; D016713:Ritanserin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000378:metabolism / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D016713:Ritanserin; D008803:Mianserin; D003533:Cyproheptadine; D002936:Cinnarizine; D007650:Ketanserin; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine; D015736:Felodipine; D011188:Potassium; D011224:Prazosin