Synthesis of a nitric oxide-like factor from L-arginine by rat serosal mast cells: stimulation of guanylate cyclase and inhibition of platelet aggregation.
Rat serosal mast cells were tested for their ability to generate a nitric oxide-like factor by two bioassay systems: inhibition of platelet aggregation and stimulation of mast cell guanylate cyclase. Incubation of rat serosal mast cells with human washed platelets resulted in an inhibition of thrombin-induced platelet aggregation proportional to the number of cells. The inhibition was potentiated by superoxide dismutase (SOD) and reversed by oxyhaemoglobin (oxyHb). The inhibitory activity of mast cells was also prevented by NG-monomethyl-L-arginine (MeArg), an effect reversed by co-incubation with L-Arg but not D-Arg. When mast cells alone were stirred at 1,000 rpm, a time-dependent increase in the levels of their cGMP but not cAMP was observed. This increase was reduced by pretreatment with MeArg. The inhibitory effect of MeArg was reversed by L-Arg but not D-Arg. These results demonstrate that rat mast cells release a factor with the same pharmacological profile as NO, and that this NO-like factor is derived from L-arginine.
Salvemini
D
D
William Harvey Research Institute, St Bartholomew's Hospital Medical College, London, U.K.
Masini
E
E
Anggard
E
E
Mannaioni
P F
PF
Vane
J
J
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004789:Enzyme Activation; D006162:Guanylate Cyclase / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008407:Mast Cells / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D010975:Platelet Aggregation Inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000097:blood; D013917:Thrombin / Q000494:pharmacology
D010975:Platelet Aggregation Inhibitors; D013481:Superoxides; D009569:Nitric Oxide; D001120:Arginine; D000242:Cyclic AMP; D013482:Superoxide Dismutase; D013917:Thrombin; D006162:Guanylate Cyclase; D006152:Cyclic GMP