Apparent association of MK-801-sensitive ion channels with L-S-nitrosocysteine recognition sites in the hindlimb vasculature of the rat.
This study demonstrates that the decreases in hindquarter vascular resistance produced by the putative endothelium-derived S-nitrosothiol, L-S-nitrosocysteine, in urethane-anesthetized rats, were attenuated by a lower dose of the N-methyl-D-aspartate (NMDA) receptor ion-channel blocker, dizocilpine (MK-801, 200 microg/kg, i.v.), whereas they were augmented by a higher dose of dizocilpine (500 microg/kg, i.v.). In contrast, L-S-nitrosocysteine-induced decreases in mesenteric vascular resistance were not affected by either dose of dizocilpine. The vasodilator actions of L-S-nitrosocysteine in these beds were not affected by the competitive NMDA receptor antagonist, 2-amino-5-phosphonovaleric acid (2-AP5). The vasodilator actions of the nitric oxide (NO) donor, (Z)-1-mid R:N-methyl-N-[6(N-methylammoniohexyl)amino]mid R:diazen-1-ium-1,2-diolate (MAHMA NONOate), in these beds were not affected by dizocilpine or by 2-AP5. These findings suggest that L-S-nitrosocysteine recognition sites in hindquarter but not mesenteric beds may be associated with dizocilpine-sensitive ion-channels similar to those in NMDA receptors.
Travis
M D
MD
Department of Pharmacology, University of Iowa, Iowa City, IA 52242-1109, USA.
Lewis
S J
SJ
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006614:Hindlimb / Q000098:blood supply / Q000187:drug effects; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D026403:S-Nitrosothiols; D014655:Vascular Resistance / Q000187:drug effects* / Q000502:physiology
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D007473:Ion Channels; D009603:Nitroso Compounds; D026403:S-Nitrosothiols; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; C021315:S-nitrosocysteine; D003545:Cysteine