Adrenergic receptors: Biphasic dose responses

Agonists and antagonists of the adrenergic receptor system were assessed fo r their capacity to affect dose-response relationships across biological mo del, tissue and endpoint. U shaped dose responses were commonly reported, a ffecting multiple endpoints such as smooth muscle contraction/relaxation, m emory, blood pressure, sexual behavior, platelet aggregation, and others. I n six of the endpoints studied, mechanistic foundations of the biphasic nat ure of the dose response were established. The quantitative features of the dose-response relationships indicated that the maximum stimulatory respons es, with but one exception, were less than twofold greater than the control s. The range of stimulatory responses was generally within 10- to 1000-fold , except for the platelet aggregation endpoint where the range was 10(3) to 10(5).