The relationship of α-adrenoceptor reserve and agonist intrinsic efficacy to calcium utilization in the vasculature

Abstract

The effects of Ca 2+ channel antagonists on α-adrenoceptor-mediated vasoconstriction have been the subject of intense research and controversy. This is particularly true for α 1-adrenoceptor-mediated vasoconstriction which for full agonists is dependent on both the mobilization of intracellular Ca 2+ and the translocation of extracellular Ca 2+, and for partial agonists (or full agonists following partial irreversible α 1-adrenoceptor inactivation) is dependent solely on the translocation of extracellular Ca 2+ . Andrew Nichols and Bob Ruffolo describe a novel hypothesis and a computer model based on receptor theory to explain the mechanism involved in the interaction between α-adrenoceptor agonists and Ca 2+ channel blockers in the vasculature. They conclude that the magnitude of the stimulus delivered to the tissue by the drug-receptor complex, which is determined in large part by the intrinsic efficacy of the agonist, is the primary determinant of the degree and extent of activation of the intracellular and extracellular Ca 2+ processes by α 1-adrenoceptor agonists. Low degrees of stimulus are associated exclusively with the translocation of extracellular Ca 2+, whereas high degrees of stimulus are additionally associated with the mobilization of Ca 2+ from intracellular sites .