L- and D-S-nitroso-beta,beta-dimethylcysteine differentially increase cGMP in cultured vascular smooth muscle cells.
We examined the effects of the L- and D-isomers of S-nitroso-beta,beta-dimethylcysteine (L- and D-S-nitrosopenicillamine, 10(-7)-10(-5) M) on the guanosine 3',5'-cyclic monophosphate (cGMP) content of cultured porcine aortic smooth muscle cells and the decomposition of these stereoisomers to nitric oxide (NO). L-S-nitrosopenicillamine was a more potent generator of cGMP than D-S-nitrosopenicillamine although both stereoisomers equally decomposed to NO. The 10(-7) M concentration of L- or D-S-nitrosopenicillamine did not generate detectable amounts of NO although 10(-7) M L-S-nitrosopenicillamine but not D-S-nitrosopenicillamine generated significant amounts of cGMP. This study shows that the stereoisomeric configuration of S-nitrosopenicillamine is an important factor in its biological potency. The data suggest that the extracellular or intracellular generation of NO is not the only mechanism by which this S-nitrosothiol generates cGMP in vascular smooth muscle.
Travis
M D
MD
Department of Pharmacology, University of Iowa, Iowa City 52242-1109, USA.
Stoll
L L
LL
Bates
J N
JN
Lewis
S J
SJ
D000704:Analysis of Variance; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000032:analysis / Q000096:biosynthesis; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D009603:Nitroso Compounds / Q000378:metabolism / Q000494:pharmacology*; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D013237:Stereoisomerism; D013552:Swine
D009603:Nitroso Compounds; C105567:S-nitroso-dimethylcysteine; D009569:Nitric Oxide; D010396:Penicillamine; D006152:Cyclic GMP