Cyclic GMP stimulation by vasopressin in LLC-PK1 kidney epithelial cells is L-arginine-dependent.
The L-arginine antagonist NG-monomethyl-L-arginine has been shown to inhibit nitric oxide formation from L-arginine in endothelial cells. In the present study NG-monomethyl-L-arginine was used to assess the role of L-arginine for cyclic GMP stimulation by vasopressin in a kidney epithelial cell line (LLC-PK1). Preincubation of cells with 1 mumol/l, 10 mumol/l and 100 mumol/l NG-monomethyl-L-arginine decreased cyclic GMP stimulation at 1 mumol/l vasopressin by 25%, 71% and 90%, respectively. This inhibition by NG-monomethyl-L-arginine was markedly reduced by L-arginine (2 mmol/l) but not D-arginine (2 mmol/l). Cyclic GMP stimulation by the calcium ionophore A23187 was also inhibited by NG-monomethyl-L-arginine and enantioselectively restored by L-arginine. However, NG-monomethyl-L-arginine did not affect cyclic GMP stimulation by sodium nitroprusside that spontaneously releases nitric oxide. These results suggest that, in kidney epithelial cells, vasopressin induces nitric oxide formation from L-arginine leading to activation of soluble guanylate cyclase. It is concluded that nitric oxide formation from L-arginine is not only responsible for endothelium-dependent relaxation but may be a more general pathway with regulatory function for intracellular guanylate cyclase activity.
Schröder
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H
Institut für Pharmakologie der Heinrich-Heine-Universität Düsseldorf, Federal Republic of Germany.
Schrör
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D001120:Arginine / Q000494:pharmacology / Q000502:physiology*; D000001:Calcimycin / Q000494:pharmacology; D002460:Cell Line; D006152:Cyclic GMP / Q000494:pharmacology*; D004847:Epithelial Cells; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D014667:Vasopressins / Q000494:pharmacology*; D019323:omega-N-Methylarginine
D014667:Vasopressins; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D000001:Calcimycin; D001120:Arginine; D006152:Cyclic GMP