Mechanism of bradykinin, ADH, and cAMP interaction in rabbit cortical collecting duct.
Vasopressin (ADH) and bradykinin (BK) have been shown to stimulate prostaglandin synthesis in rabbit cortical collecting tubules. We studied ADH and BK effects on osmotic water flow (Lp), Na transport (JNa), and transepithelial voltage (VT). Bath BK but not lumen BK blunted subsequent ADH hydroosmotic responses. This BK effect was prevented by ibuprofen or pertussigen pretreatment and was overcome with exogenous cAMP, suggesting that BK, via prostaglandins, interferes with ADH action on Lp at the cAMP generation step. In contrast, bath BK had no effect on bath-to-lumen (Jb-1Na) or lumen-to-bath (Jl-bNa) Na flux or on VT. As reported by others, ADH lowered Jl-bNa and depolarized VT; however, prostaglandin synthesis inhibitors neither prevented nor reversed these ADH effects. Together, these BK and ADH data do not support regulation of JNa by peptide-stimulated prostaglandins. Moreover, cAMP alone depolarized VT but had no effect on Jl-bNa. Therefore, ADH-induced depolarization of VT may at least partly owe to cAMP effects on VT independent of accompanying changes in JNa. As with Lp, bath BK blunted subsequent ADH effects on VT and, to a lesser extent, Jl-bNa; these BK effects on ADH action were also prevented by ibuprofen or pertussigen pretreatment. The data are consistent with the following model: 1) ADH depolarizes VT and increases Lp via cAMP; 2) ADH decreases JNa via neither cAMP nor prostaglandins; and 3) BK, via prostaglandins, inhibits the actions of ADH on Lp and VT at the inhibitory guanyl-nucleotide regulatory subunit of adenylate cyclase.
D037361:Adenylate Cyclase Toxin; D000818:Animals; D001696:Biomechanical Phenomena; D001920:Bradykinin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000494:pharmacology*; D004347:Drug Interactions; D004594:Electrophysiology; D005260:Female; D007052:Ibuprofen / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007684:Kidney Tubules / Q000187:drug effects*; D007685:Kidney Tubules, Collecting / Q000187:drug effects* / Q000378:metabolism; D037342:Pertussis Toxin; D011817:Rabbits; D012964:Sodium / Q000378:metabolism; D014667:Vasopressins / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D014867:Water / Q000378:metabolism
D037361:Adenylate Cyclase Toxin; D010566:Virulence Factors, Bordetella; D014867:Water; D014667:Vasopressins; D012964:Sodium; D000242:Cyclic AMP; D037342:Pertussis Toxin; D001920:Bradykinin; D007052:Ibuprofen; D007213:Indomethacin