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

Craig B. Neylon, Roger J. Summers

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Abstract

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. 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%. 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. 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. 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. 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. 1987 British Pharmacological Society

Original languageEnglish
Pages (from-to)367-376
Number of pages10
JournalBritish Journal of Pharmacology
Volume91
Issue number2
DOIs
Publication statusPublished - 1 Jan 1987

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