Stimulation of α 1 ‐adrenoceptors in rat kidney mediates increased inositol phospholipid hydrolysis

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