Demonstration of proximal tubular alpha-adrenoceptors in vivo

Receptors for parathyroid hormone (PTH) in the renal tubule are coupled to adenylate cyclase stimulation. PTH causes a rise in urinary cAMP by leakage from adenylate cyclase stimulation. PTH causes a rise in urinary cAMP by leakage from cells of the proximal convoluted tubule. The effects of alpha-adrenergic agonists and antagonists on the urinary cAMP response to PTH were investigated in anaesthetized rats in vivo. Injection of PTH (15 u/kg i.v.) produced an increase in urinary cAMP from 1.7 (s.e.m. = 0.3, n = 6) to 7.47 (s.e.m. = 0.7, n = 6) nmol cAMP/mumol creatinine in 30 min urine samples. Infusion of the alpha 2-adrenoceptor agonist clonidine at 1 microgram/kg per min caused a decrease in the cAMP response to PTH to 3.6 (s.e.m. = 0.5, n = 12) nmol cAMP/mumol creatinine. Infusion of the alpha 2-selective catecholamine alpha-methylnoradrenaline (1 microgram/kg per min) caused a similar reduction in urinary cAMP response to that observed with clonidine. The alpha-adrenoceptor antagonist phentolamine (100 micrograms/kg per min) enhanced the cAMP response to PTH and reversed the decreased response caused by clonidine. These results demonstrate the presence of alpha-receptors in the rat proximal convoluted tubule which oppose the actions of PTH in vivo.