Evidence for dual adrenergic receptor regulation of ovine pineal function.

Both alpha 1- and beta-adrenergic receptors are present on ovine pineals. In the rat these two receptors interact so that activation of the alpha 1-receptor potentiates the beta-receptor-mediated changes in cyclic AMP and the correlated changes in pineal N-acetyltransferase (EC 2.3.1.87). Here we investigate possible interactions between alpha 1- and beta-receptors through changes in cyclic AMP and assess the importance of each receptor to the melatonin response in ovine pineal punches/slices in vitro. The adrenergic agonists isoproterenol (ISO), noradrenaline (NA), and phenylephrine (PHE) stimulated dose-dependent changes in cyclic AMP with the order of potency of ISO greater than NA greater than PHE, consistent with their relative binding affinities for the beta-receptor. The beta-receptor antagonist, propranolol, showed dose-dependent inhibition of the ISO effect, whereas the alpha 1-selective antagonist, prazosin, had no effect. The S-shape of the stimulation and inhibition curves for ISO reflects cyclic AMP changes mediated by the beta-receptor only without interaction through the alpha 1-receptor. Each of the adrenergic agonists stimulated indistinguishable dose-dependent increases in melatonin release. The ability of PHE to stimulate changes in melatonin release in the absence of concomitant changes in cyclic AMP indicates an important role for the alpha 1-receptor. Prazosin inhibits this response, substantiating this conclusion. However, as propranolol is also inhibitory, it seems that the alpha 1-receptor response is absolutely dependent upon a small level of beta-receptor stimulation, thus providing evidence for adrenergic receptor interaction at a step other than cyclic AMP.