AVP-induced Ca fluxes and contraction of rat glomerular mesangial cells.
Arginine vasopressin (AVP) is known to exert Ca mobilization and contraction in glomerular mesangial cells and vascular smooth muscle cells. However, the relationship between changes in intracellular Ca and transmembrane Ca fluxes is not clear at the present time. Therefore, this study was undertaken to determine the effect of AVP on cytosolic calcium ([Ca2+]i) and Ca fluxes as estimated by measurements of 45Ca2+ efflux. Changes of [Ca2+]i in response to AVP were directly measured in monolayers of adherent cultured mesangial cells. AVP induced rapid concentration-dependent increases in [Ca2+]i and Ca2+ efflux. AVP also induced contraction of mesangial cells. This effect was blocked only by the V1 (pressor)-antagonist, d(CH2)5Tyr(Me)AVP. Stimulation of Ca2+ efflux and changes in [Ca2+]i by AVP completely desensitized the mesangial cells to a subsequent identical challenge of AVP with no cross-tachyphylaxis to other hormones. Even in Ca2+-free medium, AVP increased [Ca2+]i and Ca2+ efflux, but to a lesser extent. Under this condition, contraction of mesangial cells induced by AVP was also observed. Readdition of extracellular Ca2+ following the AVP-induced increase in [Ca2+]i caused a second and slower [Ca2+]i increase. In Ca2+-containing conditions, lanthanum ion-reduced AVP evoked [Ca2+]i stimulation to the value observed in Ca2+-free medium. The Ca2+ channel blocker, verapamil, partially inhibited AVP-induced Ca2+ influx but totally blocked the increase in [Ca2+]i induced by high K. Verapamil did not inhibit AVP-stimulated Ca2+ efflux and cell contraction. Dantrolene, a blocker of Ca2+ release from endoplasmic reticulum, inhibited AVP-stimulated Ca2+ efflux and cell contraction.(ABSTRACT TRUNCATED AT 250 WORDS)
Takeda
K
K
Department of Medicine, University of Colorado School of Medicine, Denver 80262.
Meyer-Lehnert
H
H
Kim
J K
JK
Schrier
R W
RW
D000634:Aminoquinolines; D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology*; D002118:Calcium / Q000493:pharmacokinetics*; D002478:Cells, Cultured; D003620:Dantrolene / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000187:drug effects* / Q000378:metabolism; D007811:Lanthanum / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014700:Verapamil / Q000494:pharmacology
D000634:Aminoquinolines; D001127:Arginine Vasopressin; D007811:Lanthanum; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-; D014700:Verapamil; D003620:Dantrolene; C035739:Quin2; D002118:Calcium