Stimulation of alpha 1-adrenoceptors in rat kidney mediates increased inositol phospholipid hydrolysis.
The molecular events which follow activation of alpha 1-adrenoceptors in rat kidney were investigated by measuring inositol phospholipid hydrolysis. Slices were labelled with [3H]-inositol (0.25 microM) and the accumulation of [3H]-inositol phosphates ([3H]-IP's) was measured after stimulation with alpha-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 microM) 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 alpha-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 greater than phenylephrine greater than methoxamine, (+)-NA. Clonidine and (-)-isoprenaline were ineffective at concentrations up to 100 microM. The order of effectiveness of alpha-adrenoceptor antagonists was prazosin greater than BE2254 greater than phentolamine greater than idazoxan greater than rauwolscine. The results indicate that alpha 1-adrenoceptors in rat kidney are linked to phosphoinositide hydrolysis and that this response is localized mainly to the renal cortex.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D005260:Female; D006868:Hydrolysis; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000502:physiology; D013403:Sugar Phosphates / Q000378:metabolism*
D000316:Adrenergic alpha-Agonists; D007295:Inositol Phosphates; D011942:Receptors, Adrenergic, alpha; D013403:Sugar Phosphates; D002118:Calcium; D009638:Norepinephrine; D007213:Indomethacin