Niguldipine discriminates between alpha 1-adrenoceptor-mediated second messenger responses in rat cerebral cortex slices.
The effect of both isomers of niguldipine, a highly selective alpha 1-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 beta-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 alpha 1-adrenoceptors mediating IP accumulation and cyclic AMP potentiation are different.
Robinson
J P
JP
Department of Physiology and Pharmacology, University of Nottingham Medical School.
Kendall
D A
DA
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism; D004095:Dihydropyridines / Q000494:pharmacology*; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D017275:Isradipine; D009638:Norepinephrine / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D015290:Second Messenger Systems / Q000187:drug effects*; D013237:Stereoisomerism
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D007295:Inositol Phosphates; D011725:Pyridines; D011942:Receptors, Adrenergic, alpha; D000242:Cyclic AMP; D007545:Isoproterenol; D009638:Norepinephrine; D017275:Isradipine; C054074:niguldipine