Inositol phospholipid hydrolysis and potentiation of cyclic AMP formation by noradrenaline in rat cerebral cortex slices are not mediated by the same alpha-adrenoceptor subtypes.
A pharmacological study was undertaken to determine whether the noradrenaline-stimulated breakdown of inositol phospholipids and the potentiation of isoprenaline-stimulated cyclic AMP by noradrenaline in rat cerebral cortex slices are mediated by the same alpha-receptor subtype. The rank order of potency of a range of alpha 1 and alpha 2 antagonists suggests that both responses may involve an alpha 1 receptor, but there were several differences between the pharmacological profiles for the two systems. Although in both cases, all selective alpha 1 antagonists were more potent than alpha 2 antagonists, the rank orders and the absolute potencies differed for the two responses. The inhibition of the inositol phosphate response was characterised by a high alpha 1/alpha 2 antagonist ratio, and in most cases, Hill slopes of inhibition were consistent with the involvement of a single receptor site. Inhibition of the cyclic AMP response had a much lower alpha 1/alpha 2 antagonist ratio and generally exhibited Hill slopes less than one. Evidence has been provided suggesting that adenosine is involved in the potentiation of cyclic AMP and that other, as yet unidentified, factors may also be involved. Even in the absence of an adenosine component, the results presented support the suggestion that the potentiation due to noradrenaline is mediated by a receptor whose identity does not easily fit with the currently accepted classification of alpha adrenoceptors.
Robinson
J P
JP
Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre, Nottingham, England.
Kendall
D A
DA
D000241:Adenosine / Q000037:antagonists & inhibitors / Q000502:physiology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003000:Clonidine / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis*; D006868:Hydrolysis; D007295:Inositol Phosphates / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000031:analogs & derivatives / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D013403:Sugar Phosphates / Q000378:metabolism*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D007295:Inositol Phosphates; D011942:Receptors, Adrenergic, alpha; D013403:Sugar Phosphates; D015016:Yohimbine; C024884:6-fluoronorepinephrine; D013806:Theophylline; D000242:Cyclic AMP; C028322:8-phenyltheophylline; D000241:Adenosine; D007545:Isoproterenol; D003000:Clonidine; D009638:Norepinephrine