Inositol Phospholipid Hydrolysis and Potentiation of Cyclic AMP Formation by Noradrenaline in Rat Cerebral Cortex Slices Are Not Mediated by the Same ?-Adrenoceptor Subtypes

Abstract

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 α-receptor subtype. The rank order of potency of a range of α₁ and α₂ antagonists suggests that both responses may involve an α₁ receptor, but there were several differences between the pharmacological profiles for the two systems. Although in both cases, all selective α₁ antagonists were more potent than α₂ 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 α₁/α₂ 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 α₁/α₂ 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 α adrenoceptors.