Stereoselective actions of S-nitrosocysteine in central nervous system of conscious rats

Am J Physiol. 1997 May;272(5 Pt 2):H2361-8. doi: 10.1152/ajpheart.1997.272.5.H2361.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blood Pressure / drug effects
  • Central Nervous System / drug effects*
  • Cysteine / analogs & derivatives*
  • Cysteine / pharmacology
  • Cystine / pharmacology
  • Dose-Response Relationship, Drug
  • Glutathione / analogs & derivatives
  • Glutathione / pharmacology
  • Heart Rate / drug effects
  • Hemodynamics / drug effects
  • Injections, Intraventricular
  • Male
  • Nitric Oxide / metabolism
  • Nitroso Compounds / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • S-Nitrosoglutathione
  • S-Nitrosothiols*
  • Stereoisomerism
  • Wakefulness

Substances

  • Nitroso Compounds
  • S-Nitrosothiols
  • Nitric Oxide
  • Cystine
  • S-Nitrosoglutathione
  • S-nitrosocysteine
  • Glutathione
  • Cysteine