Bradykinin B2 type receptor activation regulates fluid and electrolyte transport in the rabbit kidney.
Bradykinin is an important autacoid produced in the kidney, regulating both renal function and blood pressure. In vivo studies in anesthetized rabbits, revealed that BK induced diuresis (UV), natriuresis (U(Na)V) and was not associated with renal hemodynamic changes. These diuretic and natriuretic effects were blocked by the BK-B2 antagonist HOE-140. BK also inhibits vasopressin (AVP)-stimulated water flow (L(p)) in microperfused rabbit cortical collecting ducts (rCCD), in a concentration-dependent fashion, consistent with its in vivo diuretic effects. BK-B1 antagonist Leu8-des-Arg9-BK did not alter the effect of BK on Lp, but HOE-140 completely blocked the inhibitory effects of BK on Lp. While BK did not increase [Ca2+]i in fura-2 loaded freshly microdissected rCCD, BK increased [Ca2+]i in immortalized cultured rCCD cells demonstrating different signaling mechanisms are activated by BK in microdissected versus cultured rCCD. In microperfused rCCD, neither the protein kinase C inhibitor staurosporine nor the phospholipase C (PLC) inhibitor U-73,122 attenuated the BK response arguing against activation of PLC/PKC by BK in rCCD. We conclude: (1) BK induces UV and U(Na)V by a BK-B(2) receptor; (2) BK inhibits AVP-stimulated Lp by a BK-B2 receptor suggesting that its effects on Lp are not via a PLC/PKC; (3) finally, BK raises [Ca2+]i in rCCD cells by a BK-B2 receptor mechanism.
Hébert
Richard L
RL
Department of Cellular and Molecular Medicine, Kidney Research Centre, Faculty of Medicine, 451 Smyth Road, Room 1337, University of Ottawa, Ottawa, Ont., Canada K1H 8M5. rlherbert@uottawa.ca
Regoli
Domenico
D
Xiong
Huaqi
H
Breyer
Matthew D
MD
Plante
Gérard E
GE
D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D001826:Body Fluids / Q000187:drug effects / Q000378:metabolism*; D001920:Bradykinin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D065094:Bradykinin B2 Receptor Antagonists; D002478:Cells, Cultured; D004573:Electrolytes / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D011817:Rabbits; D043782:Receptor, Bradykinin B2 / Q000378:metabolism*; D013997:Time Factors
D065094:Bradykinin B2 Receptor Antagonists; D004573:Electrolytes; D043782:Receptor, Bradykinin B2; C065679:icatibant; D001920:Bradykinin