Alpha 1 B- but not alpha 1 A-adrenoceptors mediate inositol phosphate generation

We used novel highly subtype-selective antagonists to study whether alpha 1A- and/or alpha 1B-adrenoceptors mediate the stimulation of inositol phosphate generation by noradrenaline in rat cerebral cortex. Phentolamine (10 microM) and prazosin (100 nM) completely abolished the stimulated inositol phosphate generation. The alpha 1A-selective antagonists 5-methyl-urapidil (100 nM) and (+)- and (-)-niguldipine (10 nM) caused only weak inhibition or none at all although these concentrations occupied alpha 1A-adrenoceptors almost completely. In contrast, pretreatment with the irreversible alpha 1B-selective chloroethylclonidine reduced the noradrenaline-stimulated inositol phosphate generation by 76 +/- 8%. These data demonstrate that alpha 1B-adrenoceptors couple to inositol phosphate generation; the signal transduction system of alpha 1A-adrenoceptors remains unclear.