EXAMINATION OF MEDULLARY ALPHA(2) RECEPTORS IN CONNECTION WITH VERAPAMIL INDUCED-HYPOTENSION

The interaction of the phenylalkylamine calcium channel blocker, verap amil, at the alpha(2) receptor in the cat brain was studied using radi oligand binding and physiological techniques. Specific binding for [H- 3]yohimbine, a probe for the alpha, receptor, was demonstrated in the medulla. The affinity and density of [H-3]yohimbine sites were 1.62 Nm and 47 fmol/mg, respectively. Desmethoxyverapamil and the isomers of verapamil were able to displace specific [H-3]yohimbine binding. Affin ity estimates were 150 Nm for desmethoxyverapamil, 150 Nm for (-)verap amil and 480 Nm for (+)verapamil. We could not detect the presence of [H-3]desmethoxyverapamil binding sites in the medulla. To assess the p ossible physiological role of binding at the alpha(2) receptor in the medulla, verapamil was administered by the intracisternal route in the chloralose/urethane anesthetized cat and the effect on cardiovascular activity was determined. Verapamil (100-1000 nmol) was found to cause hypotension. Pretreatment with yohimbine (100 mu g) did not block the verapamil-induced hypotension. The results demonstrate that central a dministration of verapamil has a hypotensive action. However, this eff ect does not appear to be due to an interaction at alpha(2) receptors.