Stereoselective actions of S-nitrosocysteine in central nervous system of conscious rats.
This study examined whether the stereoselective actions of S-nitrosocysteine (SNC) in the central nervous system involves the activation of stereoselective SNC recognition sites. We examined the effects produced by intracerebroventricular injection of the L- and D-isomers of SNC (L- and D-SNC) on mean arterial blood pressure, heart rate, and vascular resistances in conscious rats. We also examined the hemodynamic effects produced by intracerebroventricular injections of 1) L-cystine, the major non-nitric oxide (NO) decomposition product of L-SNC, 2) the parent thiols L- and D-cysteine, and 3) the bulky S-nitrosothiol L-S-nitroso-gamma-glutamylcysteinylglycine [L-S-nitrosoglutathione, (L-SNOG)]. Finally, we examined the decomposition of L- and D-SNC and L-SNOG to NO on their addition to brain homogenates. The intracerebroventricular injection of L-SNC (250-1,000 nmol) produced falls in mean arterial pressure, increases in heart rate, and a dose-dependent pattern of changes in hindquarter, renal, and mesenteric vascular resistances. The intracerebroventricular injections of D-SNC, L-cystine, and L-SNOG produced only minor effects. The intracerebroventricular injection of L-cysteine produced pressor responses and tachycardia, whereas D-cysteine was inactive. L- and D-SNC decomposed equally to NO on addition to brain homogenates. L-SNOG decomposed to similar amounts of NO as L- and D-SNC. These results suggest that SNC may activate stereoselective SNC recognition sites on brain neurons and that S-nitrosothiols of substantially different structure do not stimulate these sites. These recognition sites may be stereoselective membrane-bound receptors for which L-SNC is the unique ligand.
Davisson
R L
RL
Cardiovascular Center, University of Iowa, Iowa City 52242, USA.
Travis
M D
MD
Bates
J N
JN
Johnson
A K
AK
Lewis
S J
SJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects*; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003553:Cystine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000031:analogs & derivatives / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007276:Injections, Intraventricular; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D009603:Nitroso Compounds / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D026422:S-Nitrosoglutathione; D026403:S-Nitrosothiols; D013237:Stereoisomerism; D014851:Wakefulness
D009603:Nitroso Compounds; D026403:S-Nitrosothiols; D009569:Nitric Oxide; D003553:Cystine; D026422:S-Nitrosoglutathione; C021315:S-nitrosocysteine; D005978:Glutathione; D003545:Cysteine