Direct renal tubular action of adrenoceptive drugs

Abstract

It has been well established that the renal nerve plays an important role in the regulation of the tubular functions. The direct renal tubular actions of adrenoceptive agonists and antagonists were examined by using isolated rabbit nephron fragments. Isoproterenol (ISO)-sensitive adenylate cyclase activity was demonstrated most prominently in the connecting tubule (CNT) and moderately in the cortical collecting tubule (CCT). By the in vitro microperfusion technique, ISO was shown to decrease the lumen negative transepithelial voltage (Vt) in the CNT and CCT. These findings suggest that β-adrenoceptors are located in these nephron segments. When 2×10−4M (±)-propranolol (PPL) was added to the bath, the Vt was suppressed sharply in association with the suppression of Na transport. This effect was attributed to the membrane stabilizing action of this drug. When tubular fragments were incubated with 10−8M [3H]-dihydroalprenolol (DHA), the tubular binding of the ligand displaced by an excess of (±)-PPL was observed in the distal nephron segments. This binding was not specific for S-adrenoceptors and was displaced only by the 8-blockers with membrane stabilizing action. In addition, affinity of the CCT to [3H]-DHA was extremely low (Kd=4.31×10−7M). By contrast, the specific binding of [3H]-prazosin was found in the proximal convoluted tubule, but not in the proximal straight tubule or CCT. These observations support the view that aj-adrenoceptors are distributed in the proximal convoluted tubule,while β-adrenoceptors are in the CNT and CCT. The data also shows the β-blockers with membrane stabilizing action inhibit Na transport by directly acting on the distal nephron segments.