Kinetics of response to epinephrine of isolated rabbit ear

Abstract

A theory for the response of the isolated rabbit ear to various concentrations of catecholamines, based on the reversible formation of a drug-receptor complex, is presented. For application of such a theory the response measured must be primary. The response measured is the increase in driving pressure required to maintain a constant flow of perfusate when a pressor drug is added. This, with a slight correction, is proportional to vascular smooth muscle tension. The agreement between results (50 curves) and theory is very good. For the reaction the over-all equilibrium constant, K, is 8.19 x 106 (S.E.M. = 1.28 x 106), ΔF° = –9.4 Kcal and, from the change in K with temperature, ΔH = 14.5 Kcal; values within the normal biological range. A negative correlation between K and the maximum response of the preparations suggests that the reaction may consist of two, or more, steps. The equilibrium constant for the first step, i.e. formation of the complex, can be roughly estimated as 15.8 x 106.