Alpha2-adrenoceptors and cellular cAMP levels in single nephron segments from the rat

Abstract

A functional role for the numerically predominant renal .alpha.-adrenoceptors, which in other tissues inhibit adenylate cyclase, remains undefined. The effect of .alpha.2-adrenoceptor stimulation with (-)-epinephrine (E) was examined on cell cAMP content in the isolated proximal convulated 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. .alpha.2-Adrenoceptors were activated using varying concentrations of E (37.degree. C, 2 min). .alpha.2-Adrenoceptor activation with E (5 .times. 10-7 to 5 .times. 10-6M) 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 .times. 10-6 M yohimbine or 5 .times. 10-7 M phentolamine but not by 5 .times. 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. There are .alpha.2-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.