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Stimulation of preganglionic sympathetic fibers to the superior cervical ganglia elevates the activity of pineal N-acetyltransferase. After the stimulation-induced rise in enzyme activity, a return toward baseline levels occurs whether or not nerve stimulation is continued. The ability of pineal N-acetyltransferase activity to fall in the presence of stimulation may account for the persistence of its rhythm in blinded animals.

ABSIRACT The availability of a series of semi-rigid analogs of dopamine and epinine has made it possible to investigate the conformational requirements for action on dopamine and 2-adrenergic vascular receptors. The analogs were screened for dopamine-agonist action by intra-arterial injections into the renal vascular bed and for P2-adrenergic activity by similar injections into the femoral vascular bed in dogs pretreated with phenoxybenzamine. 2-Amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene and its N-methyl derivative (analogous to the trans P rotamer of dopamine) exhibited pronounced dopamine-agonist activity and minimal 02-adrenergic activity. In contrast, the semi-rigid analog of the trans a rotamer of dopamine (2-amino-5,6-dihydroxy-1,2,3,4-tetrahydronaphthalene; A-5,6-DTN) and its N-methyl derivative exerted pronounced #2-adrenergic activity but were inactive as dopamine agonists.6,7-Dihydroxytetrahydroisoquinoline,a semirigid analog of the cis P rotamer of dopamine, did not produce renal vasodilation. These results indicate that a conformation of dopamine similar to that found in A-6,7-DTN is required for dopamine-vascular activity, while the conformation found in A-5,6-DTN is preferred for interaction with #2-adrenergic receptors. Dopamine can cause vasodilation by several mechanisms (1).Vasodilation can be induced directly by action on 32radrenergic or dopamine vascular receptors (2) and indirectly by action on receptors in autonomic ganglia (3, 4) and postganglionic sympathetic nerves (5, 6). Because the dopamine molecule is flexible and can assume a variety of conformations, it has not been possible to determine whether a specific conformation is required for each of these diverse actions. A possible approach to this problem has been provided recently by the demonstration that a semi-rigid analog of dopamine, 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (A-6,7-DTN), met all the criteria of a dopamine agonist in the canine renal and mesenteric vascular beds (7). Because the side chain of the dopamine moiety contained within A-6,7-DTN is fixed in a fully extended position with the amino group trans to the phenyl ring, these results suggested that this conformation of dopamine (trans ,B rotamer) may be required for activation of dopamine receptors. However, dopamine can exist in yet another trans conformation (trans a rotamer) as in 2-amino-5,6-dihydroxy-1,2,3,4-tetrahydronaphthalene , in which the phenyl ring has undergone a 1800 rotation about the phenyl-C-1 bond (see Fig. 1). Previous studies with certain derivatives of A-5,6-DTN indicated that they exert dopamine-like activity in the central nervous system, because they are potent emetic agents and produce gnawing behavior in mice (8, 9). Some of these analogs have also been shown to produce typical (32-adrenergic actions (10).Accordingly, we have compared the relative ,32-adrenergicThe costs of publication of this article were defrayed in part by the payment of page charges from funds made available to support the research which is the su...

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