Alpha2-adrenoceptors and cellular cAMP levels in single nephron segments from the rat.
A functional role for the numerically predominant renal alpha2-adrenoceptors, which in other tissues inhibit adenylate cyclase, remains undefined. We therefore examined the effect of alpha2-adrenoceptor stimulation with (-)-epinephrine (E) on cell cAMP content in the isolated proximal convoluted tubule (PCT), medullary and cortical thick ascending limb of Henle, and collecting tubule (MTAL, CTAL, MCT, and CCT, respectively). Parathyroid hormone (1-34 PTH), in PCT or CTAL, or arginine vasopressin (AVP), in MTAL, CTAL, MCT, or CCT, was used to activate adenylate cyclase in intact cells from these microdissected nephron segments in the presence of 3-isobutyl-1-methylxanthine (phosphodiesterase inhibitor) and propranolol. Alpha2-Adrenoceptors were activated using varying concentrations of E (37 degrees C, 2 min). Alpha2-Adrenoceptor activation with E (5 X 10(-7) to 5 X 10(-6) M) suppressed cellular cAMP stimulation by PTH by 35% in PCT and stimulation by AVP in CCT by 50%. This suppression by E in PCT and CCT was inhibited by 5 X 10(-6) M yohimbine or 5 X 10(-7) M phentolamine but not by 5 X 10(-6) M prazosin. E also suppressed cAMP stimulated by AVP in MCT, but it did not suppress the PTH-or AVP-stimulated increase in cellular cAMP in CTAL and MTAL. These studies show that there are alpha2-adrenoceptors in the rat nephron. Activation of these alpha 2-adrenoceptors can inhibit cAMP formation stimulated by PTH in PCT and by AVP in the CCT and MCT but not in the CTAL and MTAL. A pathophysiological role of altered regulation of these receptors is yet to be described.
Umemura
S
S
Marver
D
D
Smyth
D D
DD
Pettinger
W A
WA
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004837:Epinephrine / Q000494:pharmacology; D008297:Male; D009399:Nephrons / Q000032:analysis / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D013268:Stimulation, Chemical; D015016:Yohimbine / Q000494:pharmacology
D010281:Parathyroid Hormone; D011942:Receptors, Adrenergic, alpha; D001127:Arginine Vasopressin; D015016:Yohimbine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D011224:Prazosin; D004837:Epinephrine; D010646:Phentolamine