Inositol Phospholipid Hydrolysis in Rat Cerebral Cortical Slices: I. Receptor Characterisation

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Abstract
Characterization of receptor-mediated breakdown of inositol phospholipids in rat cortical slices was performed using a direct assay which involves pre-labeling with [3H]inositol. When slices were preincubated with [3H]inositol, Li greatly amplified the capacity of receptor agonists such as carbachol, noradrenaline [norepinephrine, NE] and 5-hydroxytryptamine to increase the amount of radioactivity appearing in the inositol phosphates. Using a large variety of agonists and antagonists cholinergic muscarinic, .alpha.1-adrenoceptor and histamine H1 receptors appear to be linked to inositol phospholipid breakdown in cortex. The large responses produced by receptor agonists allowed a clear discrimination between full and partial agonists as well as quantitative analysis of competitive antagonists for each receptor. Whereas carbachol and acetylcholine (in the presence of a cholinesterase inhibitor) were full agonists, oxotremorine and arecoline were only partial agonists. Very low concentrations of atropine shifted the carbachol dose-response curve to the right and allowed inhibition constants for the antagonist to be easily calculated. The nicotinic antagonist, mecamylamine, was ineffective. NE adrenaline [epinephrine] were full agonists at .alpha.1-adrenoceptors, but phenylephrine and probably methoxamine were partial agonists. Prazosin, but not yohimbine, potently and competitively antagonized the NE inositol phospholipid response. Mepyramine but not cimetidine competitively antagonized the histamine response. The potentiating effect of Li on neurotransmitter inositol phospholipid breakdown and emphasize the ease with which functional responses at a number of cortical receptors can be characterized.