Temperature immutability of adenyl cyclase-coupled β adrenergic recptors

Abstract

OBSERVATIONS from several laboratories have suggested that the well established classification of adrenergic receptors into α and β subtypes is not immutable. Several groups have reported that in isolated perfused frog hearts, stimulation of cardiac rate and contractility by catecholamines has the properties of a classical β adrenergic response when experiments are performed at warm temperatures (25°–37° C) but of an α adrenergic response when experiments are performed at cold temperatures (5°–15° C)^1–3. At warm temperatures, the order of potency of agonists in stimulating these preparations—isoproterenol>adrenaline>noradrenaline—is classical for a β adrenergic receptor. Similarly, effects of the catecholamines at warm temperatures are blocked by propranolol but not by the α adrenergic antagonist phentolamine. When the same experiments are performed at temperatures below 25° C, the order of potency of agonists is reversed to that characteristic of α adrenergic receptors. Also at lower temperatures α adrenergic antagonists such as phenoxybenzamine and phentolamine block the effects of adrenaline, whereas β adrenergic antagonists such as propranolol are ineffective. Gradations of response can be achieved by varying the temperature between 37° C and 10° C. Similar observations have been reported for the rat heart¹. Also in a dog heart–lung bypass preparation the β receptors seem to become ineffective at 15° C, whereas α receptors retain their effectiveness⁴. On the basis of such observations, Kunos et al.³ proposed that α and β adrenergic receptors may represent allosteric configurations of the same receptor macromolecule which could be modulated by among other factors, temperature.