A noradren aline sensitive adenylate cyclase in the rat limbic forebrain: preparation, properties and the effects of agonists, adrenolytics 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 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.
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000302:isolation & purification / Q000378:metabolism*; D000818:Animals; D000242:Cyclic AMP / Q000096:biosynthesis; D004298:Dopamine / Q000378:metabolism; D066298:In Vitro Techniques; D008032:Limbic System / Q000201:enzymology* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011941:Receptors, Adrenergic; D013268:Stimulation, Chemical; D013565:Sympatholytics / Q000494:pharmacology*; D014149:Tranquilizing Agents / Q000494:pharmacology*
D000067956:Adenylyl Cyclase Inhibitors; D011941:Receptors, Adrenergic; D013565:Sympatholytics; D014149:Tranquilizing Agents; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D004298:Dopamine; D009638:Norepinephrine