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  • Title: A noradren aline sensitive adenylate cyclase in the rat limbic forebrain: preparation, properties and the effects of agonists, adrenolytics and neuroleptic drugs.
    Author: Horn AS, Phillipson OT.
    Journal: Eur J Pharmacol; 1976 May; 37(1):1-11. PubMed ID: 179826.
    Abstract:
    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 homogenising medium. Some of its properties resemble those reported previously by other workers, using slices. Its response to agonists show that it has the characteristics of a beta1-receptor i.e. the potency of 1-isoprenaline exceeds that of 1-noradrenaline which exceeds that of 1-adrenaline. Structure--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 1-noradrenaline is sensitive to stereoselective inhibition by 1-propranolol. The effect of a number of neuroleptic drugs was examined. Promazine was the most effective agent tested in antagonising the stimulation produced by 50 muM 1-noradrenaline, whilst the potent dopamine receptor antagonist, alpha-flupenthixol was only weakly active. Furthermore, there was no stereoselectivity in the antagonism produced by alpha- and beta-siomers of flupenthixol. Pimozide was not found to be a potent antagonist. Thus 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.
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