Temperature-induced interconversion of alpha-and beta-adrenoceptors in the frog heart

1. The effect of ambient temperature on the properties of adrenoceptors mediating inotropic responses was assessed in isolated frog hearts on the basis of the effects and tissue uptake of alpha- and beta-adrenoceptor antagonists. 2. At temperatures of 23degree C and above inotropic responses to adrenaline were antagonized by propranolol (0-4-4-0muM), but were unaffected by phentolamine (26-5muM) and were potentiated by phenoxybenzamine (POB) (0-7-29-5muM). Below 17degree C the activity of propranolol was reduced at least tenfold, and the alpha-adrenoceptor antagonists inhibited responses to both adrenaline and isoprenaline, but not those to CaCL2. 3. The responses of hearts exposed to POB at 14degree C and then tested, after thorough washing, at both 14 and 24degree C were similarly inhibited at both temperatures, i.e. the usual beta-adrenoceptor response did not appear at the higher temperature. Conversely, exposure to POB at 24degree C produced only potentiation at both test temperatures. 4. Parallel to the reciprocal changes in their blocking actions, significantly more (14C)propranolol was retained by hearts exposed at high temperatures and significantly more (3H)POB was bound to the myocardium at low temperatures. Changes in binding and in the pharmaco logical effects of both blocking agents occurred entirely within a relatively narrow temperature range (17-22degree C) Parallel to the change from alpha- to beta-adrenoceptor characteristics with increasing temperature, the sensitivity of the hearts to adrenaline increased about tenfold. 5. Phentolamine (26-5muM) effectively protected hearts from block by (3H)POB at 14degree C, unmasked a potentiation of responses to adrenaline equivalent to that produced by POB at 24degree C, and reduced binding of the label to approximately the level found in unprotected hearts exposed at the higher temperature. At 24degree C, phentolamine did not alter the potentiation produced by (3H)POB, and reduced binding only slightly. There was no significant temperature differential in the amount of (3H)POB bound in the presence of phentolamine. 6. The results presented indicate a close functional and, probably, morphological association of alpha- and beta-adrenoceptors in the frog heart. It is suggested that the two classes of adrenoceptors may represent allosterie conformations of the same structure.