Possible sites of temperature-dependent changes in sensitivity of the positive inotropic and chronotropic responses to sympathomimetic amines by comparisons of the temperature optima for a range of agonists.

The temperature optimum for the positive inotropic response of guinea-pig isolated atria to single submaximal doses of isoprenaline was 25 degrees C. This was well separated from that for rate responses (37.5 degrees C). This separation was not due to changes in catechol-0-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, calcium chloride and dibutyryl cAMP were essentially the same as for isoprenaline. The temperature-dependences therefore 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 also eliminated as possible sites from differing optima of aminophylline, histamine and dibutyryl cAMP. The temperature-dependence may lie at the beta-adrenoceptor itself, possibly adenyl cyclase. This may be shared by glucagon although tachyphaylaxis made its optimum difficult to determine.