AJP - Gastrointestinal and Liver Physiology, Vol 254, Issue 4 586-G594, Copyright © 1988 by American Physiological Society
Ca2+ channel blockers interact with alpha 2-adrenergic receptors in rabbit ileum
F. R. Homaidan, M. Donowitz, J. Wicks, S. Cusolito, M. E. el Sabban, G. A. Weiland and W. G. Sharp
Department of Pharmacology, New York State College of Veterinary Medicine, Cornell University, Ithaca 14853.
An interaction between Ca2+ channel blockers and alpha 2-adrenergic
receptors has been demonstrated in rabbit ileum by studying the effect of
clonidine on active electrolyte transport, under short-circuited
conditions, in the presence and absence of several Ca2+ channel blocking
agents. Clonidine, verapamil, diltiazem, cadmium, and nitrendipine all
decrease short-circuit current and stimulate NaCl absorption to different
extents with clonidine having the largest effect. Exposure to verapamil,
diltiazem, and cadmium inhibited the effects of clonidine on transport,
whereas nitrendipine had no such effect. Verapamil, diltiazem, and cadmium,
but not nitrendipine, also decreased the specific binding of [3H]alpha
2-adrenergic agents to a preparation of ileal basolateral membranes
explaining the observed decrease in the transport effects of clonidine. The
effective concentrations of the Ca2+ channel blockers that inhibited the
effects of clonidine on transport were fairly similar to the concentrations
needed to inhibit its specific binding. The displacement of clonidine by
calcium channel blockers is ascribed to a nonspecific effect of these
agents, although the possibility that their effects are exerted via their
binding to the calcium channels is not excluded.
