NORADRENALINE SENSITIVE ADENYLATE-CYCLASE IN RAT LIMBIC FOREBRAIN - PREPARATION, PROPERTIES AND EFFECTS OF AGONISTS, ADRENOLYTIC AND NEUROLEPTIC DRUGS

A method for the preparation of a noradrenaline sensitive adenylate cyclase from homogenates of the rat limbic forebrain is described using Krebs-Ringer as the homogenizing medium. Some of its properties resemble those previously reported using slices. Its response to agonists shows that it has the characteristics of a .beta.1-receptor i.e., the potency of l-isoprenaline exceeds that of l-noradrenaline which exceeds that of l-adrenaline. Structure.sbd.activity analysis of the response of the adenylate cyclase to a range of adrenergic agonists shows a strict requirement for a catechol moiety and a .beta.-hydroxyl group. The activation of the enzyme by l-noradrenaline is sensitive to stereoselective inhibition by l-propranolol. The effect of a number of neuroleptic drugs was examined. Promazine was the most effective agent tested in antagonizing the stimulation produced by 50 .mu.M l-noradrenaline, while the potent dopamine receptor antagonist, .alpha.-flupenthixol was only weakly active. There was no stereoselectivity in the antagonism produced by .alpha.- and .beta.-isomers of flupenthixol. Pimozide was not a potent antagonist. The spectrum of antagonism produced by neuroleptic drugs was quite different from that seen in the dopamine sensitive adenylate cyclase of the rat corpus striatum.