Renal proximal tubular alpha-adrenergic receptors oppose urinary 3,5'-cyclic adenosine monophosphate response to parathyroid hormone in vivo.
In both man and rat, urinary cAMP (U cAMP) level increases in response to PTH. The increased cAMP arises largely by secretion from the proximal tubule where cAMP synthesis is stimulated by PTH through adenylate cyclase-coupled receptors. We have previously demonstrated alpha 2-adrenergic receptors which inhibit PTH-stimulated adenylate cyclase in rat renal cortex membranes in vitro. In the present study, the effects of alpha-adrenergic agonists and antagonists on the U cAMP response to PTH were investigated in anesthetized rats in vivo. Injection of PTH (15 U/kg iv) produced an increase in U cAMP from 1.7 +/- 0.3 to 7.4 +/- 0.7 nmol cAMP/mumol creatinine (n = 6), (P less than 0.001). This rise was largely due to an increase in nephrogenous cAMP which increased 10-fold. Infusion of the alpha 2-adrenergic agonist clonidine at 1 microgram/kg X min caused a decrease in the cAMP response to PTH to 3.6 +/- 0.5 nmol cAMP/mumol creatinine (n = 12) (P less than 0.001). Infusion of the alpha 2-selective catecholamine alpha-methylnorepinephrine (1 microgram/kg X min) caused a similar reduction in U cAMP response to that observed with clonidine. The alpha-adrenergic antagonist phentolamine (100 micrograms/kg X min) reversed the effects of clonidine and, when administered in the absence of alpha-agonists, caused an increased cAMP response to PTH. These results demonstrate the presence of alpha-receptors in the rat proximal convoluted tubule which oppose the actions of PTH in vivo.
Woodcock
E A
EA
Johnston
C I
CI
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000768:Anesthesia, General; D000818:Animals; D000242:Cyclic AMP / Q000652:urine*; D007687:Kidney Tubules, Proximal / Q000502:physiology*; D008297:Male; D010281:Parathyroid Hormone / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D010281:Parathyroid Hormone; D011942:Receptors, Adrenergic, alpha; D000242:Cyclic AMP