Niguldipine discriminates between α1-adrenoceptor-mediated second messenger responses in rat cerebral cortex slices

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Abstract
The effect of both isomers of niguldipine, a highly selective α1-adrenoceptor antagonist and dihydropyridine calcium channel blocker, on noradrenaline-stimulated inositol phosphate (IP) accumulation and adenosine 3′:5′-cyclic monophosphate (cyclic AMP) potentiation was examined. Both isomers inhibited noradrenaline-stimulated IP accumulation. (+)-Niguldipine was 100 fold more potent than (−)-niguldipine. Potentiation of β-adrenoceptor-stimulated cyclic AMP by noradrenaline was only partially inhibited by both isomers. The dihydropyridine, israpidine, did not inhibit either second messenger response. This study provides further evidence that the α1-adrenoceptors mediating IP accumulation and cyclic AMP potentiation are different.