RT Journal Article SR Electronic T1 Supersensitivity in Rat Cerebral Cortex: Pre- and Postsynaptic Effects of 6-Hydroxydopamine at Noradrenergic Synapses JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 1170 OP 1180 VO 13 IS 6 A1 JONATHAN R. SPORN A1 BARRY B. WOLFE A1 T. KENDALL HARDEN A1 PERRY B. MOLINOFF YR 1977 UL http://molpharm.aspetjournals.org/content/13/6/1170.abstract AB The intraventricular administration of 6-hydroxydopamine resulted in the destruction of noradrenergic nerve terminals in the rat cerebral cortex and a 90% decrease in norepinephrine content. The time courses of the effects of this treatment on catecholamine-stimulated cyclic 3',5'-AMP accumulation in slices of cerebral cortex and on beta adrenergic receptors were determined to investigate the mechanisms underlying supersensitivity in this system. The EC50 for norepinephrine stimulation of cyclic AMP accumulation decreased following 6-hydroxydopamine administration. This decrease was apparent within 1 day and was probably due to the loss of the presynaptic uptake system for norepinephrine. The density of beta adrenergic receptors, as determined by measuring the binding of the high-affinity beta adrenergic receptor antagonist [125I]iodohydroxybenzylpindolol, and maximal levels of catecholamine-stimulated cyclic AMP accumulation increased with a slower time course, reaching peak levels approximately 16 days after treatment with 6-hydroxydopamine. The maximal increase in the density of beta adrenergic receptors was 50%, while maximal levels of cyclic AMP accumulation in treated rats were approximately twice those measured in control animals. The KD of [125I]iodohydroxybenzylpindolol for beta adrenergic receptors and the EC50 of isoproterenol for stimulation of cyclic AMP accumulation were unchanged following 6-hydroxydopamine administration, suggesting that the intrinsic properties of the postsynaptic receptor were not affected by denervation. The administration of 6-hydroxydopamine did not affect fluoride-sensitive adenylate cyclase activity. The results are consistent with the idea that the supersensitivity to catecholamines that occurs in the cerebral cortex following 6-hydroxydopamine administration had both pre- and postsynaptic components. The slowly developing postsynaptic component can be at least partially explained by an increase in the density of beta adrenergic receptors. ACKNOWLEDGMENT Ms. Jane Andrews provided excellent technical assistance.