Influence of temperature on the sensitivity of the ?-receptors and the contractility of guinea-pig atrium

Temperature‐induced changes in dissociation constants (KA) of agonists at cardiac β‐adrenoceptors determined by use of the irreversible antagonist Ro 03–7894

“…This finding would seem at variance with that obtained with 13-adrenoceptor antagonists. The affinities of antagonists, measured as the pA2 value, have been shown to remain unaltered at different temperatures in guinea-pig (Reinhardt et al, 1972) and mouse atria (Munioz-Ramirez, Ryan & Buckner, 1975). This anomaly may be explained by observations from P-adrenoceptor binding studies, which indicate a difference in the interaction of agonists and antagonists with the f-adrenoceptor (Williams & Lefkowitz, 1977).…”

“…Since there is no change in the affinity of fiadrenoceptor antagonists, as measured by pA2 values, when temperature is lowered (Reinhardt et al, 1972), it would appear unlikely that an increase in the affinity of sympathomimetic amines could account for their change in potency with hypothermia. However, it has recently been shown that the kinetics of agonist and antagonist binding are different (Weiland, Minneman & Molinoff, 1979;1980) and the possibility that the supersensitivity may be the result of an increase in affinity of agonists only, must be considered.…”

Temperature-Dependence of Maturation of Chronotropic and Inotropic Responses to Isoproterenol

“…Reinhardt et al [26] dem onstrated that cooling guinea pig atria shifted the dose-response curves to isoproterenol to the left and increased the maximal developed tension while decreasing the rate of tension development. These findings are sim ilar to ours in terms of the sensitivity and tension development in response to isoproterenol.…”

“…It is established that low temperatures induce supersensitivity to cate cholamines in adult cardiac tissues for both inotropic [7,11,21,22,26,30,34] and chronotropic [7,11,19,22] responses. Reinhardt et al [26] dem onstrated that cooling guinea pig atria shifted the dose-response curves to isoproterenol to the left and increased the maximal developed tension while decreasing the rate of tension development.…”

“…Matura tion of beta-adrenoceptor sensitivity may be tissue-specific, i.e., sinus node beta-adrenoceptors may develop in number and sensitivity sooner than those in the myocardium, despite the similarity in receptor subtype classi fication [3], A second possibility relates to differences in temperature at which beta-adrenoceptor sensitivity was examined. Ventricular tissues are usually studied at low temperatures to reduce problems deriving from tis sue thickness [25,28,29,33], It is known that cooling raises the inotropic sensitivity of adult ventricular tissues to adrenergic agents [7,11,19,20], As the thinner atrial tissue is not as subject to the above diffusion problems [7,26], studies of atrial chronotropic or inotropic sensitivity to beta-adre noceptor stimulation are conduceted at more physiological temperatures.…”