Stimulation of α1-adrenoceptors in rat kidney mediates increased inositol phospholipid hydrolysis

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Abstract
1 The molecular events which follow activation of α1-adrenoceptors in rat kidney were investigated by measuring inositol phospholipid hydrolysis. Slices were labelled with [3H]-inositol (0.25 μm) and the accumulation of [3H]-inositol phosphates ([3H]-IP's) was measured after stimulation with α-adrenoceptor agonists. 2 Phospholipid labelling was both time-and Ca2+-dependent. In kidney, Ca2+ (1 mm) increased the incorporation of [3H]-inositol by 49% and in cerebral cortex reduced it by 46%. 3 Following addition of noradrenaline (NA, 1 mm), accumulation of [3H]-IP's increased linearly for at least 60 min. In Ca2+-free buffers a 2.1 fold increase in [3H]-IP accumulation was observed and further increases in stimulated and control levels were produced in the presence of Ca2+ (2.5 mm). These responses were attenuated by the inclusion of indomethacin (10 μm) and abolished in the presence of EGTA (0.5 mm). Responses to (−)-NA were more than 4 fold higher in the renal cortex than in the medulla. 4 Separation of the IP's which accumulate after α-adrenoceptor agonists showed that after 60 min stimulation the major products were glycerophosphoinositol and inositol-phosphate with smaller amounts of inositol-bisphosphate and inositol-trisphosphate. 5 The most effective agonists tested for stimulation of accumulation of [3H]-IP's were (–)- NA > phenylephrine > methoxamine, (+)-NA. Clonidine and (–)-isoprenaline were ineffective at concentrations up to 100 μm. The order of effectiveness of α-adrenoceptor antagonists was prazosin > BE2254 > phentolamine > idazoxan > rauwolscine. 6 The results indicate that α1-adrenoceptors in rat kidney are linked to phosphoinositide hydrolysis and that this response is localized mainly to the renal cortex.