THE EFFECT OF CALCIUM DEPLETION ON THE COMBINATION OF AGONISTS AND COMPETITIVE ANTAGONISTS WITH ALPHA ADRENERGIC AND HISTAMINERGIC RECEPTORS OF RABBIT AORTA

¹ Department of Pharmacology, Division of Basic Health Sciences, Emory University, Atlanta, Georgia and The Lilly Research Laboratories, Indianapolis, Indiana

We studied the effect of calcium depletion on the ability of norepinephrine and phentolamine and of histamine and diphenhydramine to protect their receptors against irreversible blockade by phenoxybenzamine (POB). Half of the strips were depleted of calcium by soaking for 18 hours in a calcium-free medium containing ethylene glycol bis(-aminoethyl ether)-N, N’-tetraacetic acid (EGTA); the rest served as nondepleted controls. After exposure to POB, calcium was restored to depleted strips, and blockade was assessed by contractile responses to norepinephrine or histamine. Calcium depletion did not alter the ability of POB to block alpha adrenergic and histaminergic receptors, nor did depletion affect protection of these receptors by the competitive antagonists (phentolamine and diphenhydramine). However, protection of receptors by agonists (norepinephrine and histamine) was prevented by calcium depletion. Assay of tissue calcium by atomic absorption spectrophotometry showed that, at the time of exposure to POB, the depleted strips contained 96% less calcium than the nondepleted strips. We concluded that depletion of tissue calcium impairs the receptor interactions of norepinephrine and histamine but has no effect on the receptor interactions of phentolamine, diphenhydramine or POB.