POSSIBLE SITES OF TEMPERATURE-DEPENDENT CHANGES IN SENSITIVITY OF POSITIVE INOTROPIC AND CHRONOTROPIC RESPONSES TO SYMPATHOMIMETIC AMINES BY COMPARISONS OF TEMPERATURE OPTIMA FOR A RANGE OF AGONISTS

Abstract

The temperature optimum for the positive inotropic response of guinea pig isolated atria to single submaximal doses of isoprenaline was 25.degree. C. This was separated from that for rate responses (37.5.degree. C). This separation was not due to changes in catechol-o-methyl-transferase or phosphodiesterase activity since it occurred with orciprenaline alone and in the presence of theophylline. The rate optima for aminophylline, histamine, glucagon, ouabain, CaCl2 and dibutyryl c[cyclic]AMP were essentially the same as for isoprenaline. The temperature-dependences lie at a common ultimate pathway leading to the rate response. The site of temperature-dependence of the inotropic response to isoprenaline is not at the common contractile mechanisms since its optimum differed from those of ouabain and CaCl2. Activity of cAMP and its production were eliminated as possible sites from differing optima of aminophylline, histamine and dibutyryl cAMP. The temperature-dependence may lie at the .beta.-adrenoreceptor itself, possibly adenyl cyclase. This may be shared by glucagon although tachyphylaxis made its optimum difficult to determine.