Interaction between Ca2+, verapamil, and ketanserin in rat tail artery and aorta.
To elucidate the complex pharmacological actions of the 5-hydroxytryptamine2A (5-HT2A)-receptor antagonist ketanserin, we investigated certain similarities between these properties and those of the Ca antagonist verapamil. We investigated the interactions of Ca2+, ketanserin, and verapamil on the contractile responses to 5-HT in rat isolated perfused tail artery and aortic strip preparations. In both tissues, variations in perfusate [Ca2+] had similar effects: threshold contractile concentrations of 5-HT were unaffected, and the upper ends of the 5-HT dose-response curves were augmented or decreased by increased or decreased [Ca2+], respectively. Ketanserin competitively antagonised contractile responses to 5-HT in both tissues, with mean pA2 values of 9.17 and 7.46 in tail artery and aorta, respectively. However, increase in [Ca2+], with addition of ketanserin, caused a parallel leftward shift of the 5-HT dose-response curve in tail arteries with a nonparallel leftward shift in aorta. Verapamil nonsurmountably antagonised contractile responses to 5-HT in aorta and competitively antagonised 5-HT in tail arteries. Subsequent addition of ketanserin to the verapamil-containing perfusate caused a further shift to the right of the 5-HT dose-response curve in aorta, but had no additional antagonist effect above that of verapamil alone on tail artery responses to 5-HT. The results show that although the pharmacological properties of ketanserin and verapamil overlapped, there were marked differences between the pharmacologies of the 5-HT2A-receptors in the two tissues studied, suggesting either that the mechanism of the 5-HT-induced influx of Ca2+ is different in the two tissues or that the 5-HT2A receptors differ structurally between tissues.
Okoro
E O
EO
Clinical Pharmacology Department, Royal North Shore Hospital, St. Leonards, New South Wales, Australia.
Marwood
J F
JF
Stokes
G S
GS
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001158:Arteries / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology* / Q000502:physiology; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D013623:Tail / Q000098:blood supply; D014700:Verapamil / Q000494:pharmacology*
D018340:Receptors, Adrenergic, alpha-1; D012702:Serotonin Antagonists; D012701:Serotonin; D007650:Ketanserin; D014700:Verapamil; D002118:Calcium