Regulation of renal cellular cAMP levels by prostaglandins and alpha 2-adrenoceptors: microdissection studies.
Previous studies in our laboratory demonstrated that alpha 2-adrenoceptor activation reversed arachidonic acid induced diuresis in the rat. However, the site of action was not elucidated. Since prostaglandin E2 is the predominant prostaglandin metabolite of arachidonic acid, we studied the effect of renal alpha 2-adrenoceptor stimulation on prostaglandin E2 (PGE2) induced cAMP formation. The study was done in intact single nephron segments and glomeruli. All incubations were done in the presence of 1-methyl-3-isobutylxanthine (phosphodiesterase inhibitor) and propranolol at 37 degrees C for two minutes. PGE2 increased cellular cAMP levels in the thin descending limb of Henle (tDL), cortical collecting tubule (CCT) and glomerulus. Alpha 2-adrenoceptors were activated with varying concentrations of epinephrine (E). In the tDL, alpha 2-adrenoceptor activation with E (5 X 10(-6)M to 5 X 10(-5)M) suppressed (p less than 0.05) PGE2 stimulated cAMP production by 35%. This suppression by E was inhibited by 5 X 10(-6)M yohimbine but not by 5 X 10(-6)M prazosin confirming alpha 2-adrenoceptor mediation of the effects of E. Conversely, in the CCT and glomerulus, E had no effect on PGE2-stimulated increases in cellular cAMP levels. Thus, the capacity of alpha 2-adrenoceptors to inhibit PGE2-stimulated adenylate cyclase is anatomic site-specific. This effect of alpha 2-adrenoceptors on cAMP in the tDL may explain, at least in part, the effect of alpha 2-adrenoceptors on arachidonic acid induced diuresis in the rat.
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Umemura
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Smyth
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Pettinger
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D015232:Dinoprostone; D004210:Dissection; D004837:Epinephrine / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000648:ultrastructure; D007684:Kidney Tubules / Q000648:ultrastructure; D008297:Male; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology*; D011458:Prostaglandins E / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D015016:Yohimbine / Q000494:pharmacology
D011453:Prostaglandins; D011458:Prostaglandins E; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D011433:Propranolol; D000242:Cyclic AMP; D015232:Dinoprostone; D015056:1-Methyl-3-isobutylxanthine; D011224:Prazosin; D004837:Epinephrine