Cross-tolerance to L-arginine-dependent guanylate cyclase activators in nitrate-tolerant LLC-PK1 kidney epithelial cells.
Recently, it was shown that in LLC-PK1 kidney epithelial cells hormones such as vasopressin or oxytocin increase cyclic GMP in a receptor-mediated and L-arginine-dependent manner. In the present study, the possible existence of cross-tolerance to vasopressin and oxytocin was investigated in nitrate-tolerant LLC-PK1 cells. Pretreatment with 1 mM glyceryl trinitrate for 3 h decreased cyclic GMP stimulation by 1 microM vasopressin and 1 microM oxytocin by 49% and 54%, respectively. Under the same conditions, cyclic GMP stimulation at 1 microM sodium nitroprusside was diminished by 56% whereas the cyclic GMP response to 100 microM glyceryl trinitrate was virtually abolished. Our results demonstrate that a substantial degree of cross-tolerance to L-arginine-dependent guanylate cyclase activators occurs in nitrate-pretreated nonvascular cells which may be due to glyceryl trinitrate-induced desensitization of soluble guanylate cyclase.
Schröder
H
H
Institut für Pharmakologie, Heinrich-Heine-Universität, Düsseldorf, FRG.
Barann
M
M
Bennett
B M
BM
Leitman
D C
DC
D000818:Animals; D001120:Arginine / Q000502:physiology*; D002460:Cell Line; D006152:Cyclic GMP / Q000378:metabolism; D004361:Drug Tolerance / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D004848:Epithelium / Q000187:drug effects; D006162:Guanylate Cyclase / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects; D005996:Nitroglycerin / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D010121:Oxytocin / Q000494:pharmacology; D013552:Swine; D014667:Vasopressins / Q000494:pharmacology
D014667:Vasopressins; D009599:Nitroprusside; D010121:Oxytocin; D001120:Arginine; D006162:Guanylate Cyclase; D005996:Nitroglycerin; D006152:Cyclic GMP