COMPARATIVE REGULATION OF POTASSIUM AND AMPHETAMINE INDUCED RELEASE OF H-3-NOREPINEPHRINE FROM RAT-BRAIN VIA PRESYNAPTIC MECHANISMS

This study examined the ability of various drugs to modify the potassium (K) or d-amphetamine (d-A) induced release of 3H-norepinephrine 3HNE) from chopped rat cortical tissue. The K induced release of the transmitter, which occurs from reserpine sensitive sites of cortical tissue, was significantly reduced by the beta receptor antagonist propranolol, the alpha receptor agonist clonidine and also by PGE2. Pretreatment with eicosatetrynoic acid, an inhibitor of prostaglandin synthesis, did not influence the effect of clonidine on 3HNE release; thus this latter effect appears to be independent of enhanced prostaglandin formation. The proposed alpha receptor mediated negative feedback exhibits stereospecificity since addition of exogenous 1-, but not d-, NE decreased release of the transmitter. Blockade of alpha receptors by phentolamine or stimulation of beta receptors by isoproterenol significantly enhanced the K induced release of 3HNE from cortical tissue. By contrast, the d-A induced release of 3HNE which occurs from reserpine-insensitive sites, was reduced by propranolol and clonidine; and was not altered by phentolamine, isoproterenol or PGE2. These data indicate that the K, but no d-A, induced release of 3HNE from cortical tissue is modified in accordance with postulated presynaptic negative and positive feedback mechanisms. © 1979.