title: Vasopressin stimulates Cl- transport in ascending thin limb of Henle's loop in hamster.
abstract: The effect of arginine vasopressin (AVP) on NaCl transport was investigated in the isolated microperfused hamster ascending thin limb of Henle's loop by measuring transepithelial voltage (Vt) and transmural 22Na+ and 36Cl- fluxes. In the presence of a transmural NaCl concentration gradient (100 mM higher in the lumen), Vt was 8.4 +/- 0.4 mV. Addition of 1 nM AVP to the basolateral solution increased Vt to 9.6 +/- 0.4 mV, which corresponds to an increase in the Cl- to Na+ permselectivity ratio (PCl/PNa) from 2.8 +/- 0.2 to 3.4 +/- 0.2. AVP at physiological concentrations increased Vt in a dose-dependent manner with an ED50 of 5 pM. AVP increased the Cl- efflux coefficient from 99.6 +/- 6.3 to 131.4 +/- 10.6 x 10(-7) cm2/s without affecting the Na+ efflux coefficient. 5-Nitro-2-(3-phenyl-propylamino)-benzoate (0.2 mM), a Cl- channel inhibitor, in the perfusate decreased the basal Cl- efflux coefficient and inhibited the AVP-induced increase in this parameter. The AVP-induced increase in Vt was not affected by [d(CH2)5(1),O-Me-Tyr2,Arg8] vasopressin, a V1 receptor antagonist, but was abolished by [d(CH2)5,D-Ile2,Ile4,Arg8] vasopressin, a V2 receptor antagonist. The selective V2 agonist dDAVP in 1 nM also increased Vt from 8.6 +/- 0.7 to 9.5 +/- 0.6 mV. Dibutyryl cAMP and forskolin both increased Vt, whereas H89, an inhibitor of cAMP-dependent protein kinase, abolished the AVP-induced increase in Vt. These results demonstrate that AVP stimulates Cl- transport in the ascending thin limb of Henle's loop by activating Cl- channels via a signal transduction cascade comprising V2 receptors, adenylate cyclase, and cAMP-dependent protein kinase. The ascending thin limb of Henle's loop thus participates in the formation of concentrated urine as one of the target renal tubular segments of AVP.
authors.affiliation: Department of Clinical Biology and Hormonal Regulation, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Takahashi
authors.forename: Y
authors.initials: Y
authors.lastname: Kondo
authors.forename: O
authors.initials: O
authors.lastname: Ito
authors.forename: Y
authors.initials: Y
authors.lastname: Igarashi
authors.forename: K
authors.initials: K
authors.lastname: Omata
authors.forename: K
authors.initials: K
authors.lastname: Abe
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D001692:Biological Transport; D002463:Cell Membrane Permeability; D065101:Chloride Channel Agonists; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D006224:Cricetinae; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D066298:In Vitro Techniques; D008138:Loop of Henle / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008647:Mesocricetus; D017483:Receptors, Vasopressin / Q000378:metabolism; D015398:Signal Transduction; D012964:Sodium / Q000378:metabolism
chemical_list: D065101:Chloride Channel Agonists; D018118:Chloride Channels; D002712:Chlorides; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D012964:Sodium; D017868:Cyclic AMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases