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Comparison of the effects of dopamine and beta-adrenergic agonists on adenylate cyclase of renal glomeruli and striatum.

A dopamine-sensitive adenylate cyclase was identified in glomeruli prepared from rat kidney. The properties of central and peripheral cyclase-linked dopamine receptors were then compared by testing the ability of dopamine, isoproterenol, and the dopamine analogues, 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (A-6,7-DTN), 2-amino-5,6-dihydroxy-1,2,3,4-tetrahydronaphthalene (A-5,6-DTN), and N,N -di- n -propyl dopamine (DPDA) to stimulate cyclic AMP production in homogenates and intact cell preparations of rat striatum and glomeruli. Cyclic AMP production in striatal homogenates was increased by dopamine, A-6,7-DTN, and DPDA, although DPDA was much less potent than the other two agonists. A-5,6-DTN (0-1000 µM) and isoproterenol (0-100 µM) were without effect in this preparation. In contrast, in a homogenate of kidney glomeruli as well as in striatal slices and in the intact glomeruli, all of these agonists increased cyclic AMP production. The pharmacological character of this response was further characterized by using the dopamine antagonist, fluphenazine, and the beta -adrenergic antagonist, propranolol. In glomerular homogenates, fluphenazine (10 µM) blocks the response to A-6,7-DTN (100 µM) and dopamine (100 µM) but does not affect the response to isoproterenol (1 µM) or A-5,6-DTN (100 µM). Propranolol (100 µM), on the other hand, blocked the response to isoproterenol, A-5,6-DTN, and partially blocked the dopamine response. A similar profile of activity was observed in intact glomeruli and in striatal slices. These findings suggest that both dopaminergic and beta -adrenergic receptors can mediate the production of cyclic AMP in the rat striatum and in the kidney vasculature. It is further suggested that dopamine can activate both types of receptors, depending on its concentration. The beta -rotameric conformer of dopamine (as exemplified by the semi-rigid analogue A-6,7-DTN) preferentially activates dopamine receptors, whereas the alpha -rotameric conformer (A-5,6-DTN) preferentially activates beta -adrenergic receptors. The potency series for activation of dopamine receptors is dopamine = A-6,7-DTN > DPDA in both tissues. The relative potency for activation of the beta -adrenergic response is also similar in both tissues. On the basis of the limited series of compounds studied, the cyclase-linked receptor in kidney vasculature and that in striatum appear to be quite similar.