Arginine vasopressin and oxytocin increase intracellular calcium and cAMP in human glomerular epithelial cells in culture.
The signal transduction linkages of arginine vasopressin (AVP) and oxytocin receptors were investigated in human glomerular epithelial cells (GEC) in culture. AVP (ED50, 10(-7) mol/l) and oxytocin (ED50, 3 x 10(-8) mol/l) induced a rapid, transient and dose-dependent increase in [Ca2+]i as detected by fura-2 microfluorimetry. The baseline of [Ca2+]i in human GEC was 109 +/- 2.8 nmol/l (n = 60). The V1a receptor antagonist [d(CH2)5(1), Tyr(Me)2, Arg8]-vasopressin inhibited the AVP-(IC50, 5 x 10(-9) mol/l) and oxytocin-induced (IC50, 3 x 10(-8) mol/l) increase in [Ca2+]i in a dose-dependent manner. Both, AVP and oxytocin caused accumulation of cAMP. The AVP-stimulated cAMP increase was blocked by pretreatment of human GEC with the V1a receptor antagonist (10(-7) mol/l), whereas the oxytocin-induced cAMP accumulation remained uninfluenced. In conclusion the present results indicate that: (1) V1a receptor activation, AVP and oxytocin induce a transient elevation in [Ca2+]i in human GEC; (2) AVP and oxytocin cause cAMP accumulation; (3) the AVP-induced cAMP accumulation is inhibited by a V1a receptor antagonist, whereas (4) the oxytocin response showed no effect. In addition, a different receptor might be possible, at least in oxytocin-induced-cAMP accumulation.
Späth
M
M
Medizinische Universitätsklinik, Abteilung Innere Medizin IV, Freiburg, Deutschland.
Pavenstädt
H
H
Petersen
J
J
Schollmeyer
P
P
D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis / Q000378:metabolism*; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D007678:Kidney Glomerulus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010121:Oxytocin / Q000494:pharmacology*; D017483:Receptors, Vasopressin / Q000819:agonists; D012076:Renal Agents / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*
D065092:Antidiuretic Hormone Receptor Antagonists; D006727:Hormone Antagonists; D017483:Receptors, Vasopressin; D012076:Renal Agents; D001127:Arginine Vasopressin; D010121:Oxytocin; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-; D000242:Cyclic AMP; D003894:Deamino Arginine Vasopressin; D002118:Calcium