Production of endogenous nitric oxide and activation of soluble guanylate cyclase are required for N-methyl-D-aspartate-produced facilitation of the nociceptive tail-flick reflex.
The intrathecal (i.t.) administration of either N-methyl-D-aspartate (NMDA, 10 fmol to 10 pmol) or L-arginine (1 pmol to 10 nmol), but not D-arginine (1 pmol to 10 nmol), produced a rapid, transient, dose-dependent facilitation (maximal response of 30.9 +/- 6.0% and 33.7 +/- 1.5%, respectively) of the nociceptive tail-flick reflex (ED50 = 47.8 +/- 15.4 fmol and 11.4 +/- 2.7 pmol, respectively). Maximal NMDA-produced facilitation of the tail-flick reflex (1 pmol i.t.) was completely abolished by prior treatment (10 min prior) with either N omega-nitro-L-arginine methyl ester (L-NAME, 10 nmol i.t.), methylene blue (10 nmol i.t.) or DL-5-aminophosphonovaleric acid (AP5, 100 pmol i.t.). NMDA-produced facilitation was completely recovered 40 min after L-NAME, 50 min after methylene blue and 30 min after AP5. L-NAME, methylene blue or AP5 did not significantly alter baseline tail-flick latency. These results suggest that NMDA-produced facilitation of a thermal nociceptive reflex is mediated through activation of an NMDA receptor that results in an increase in endogenous nitric oxide and activation of soluble guanylate cyclase in lumbar spinal cord.
Department of Pharmacology, College of Medicine, University of Iowa, Iowa City 52242.
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Meller
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Dykstra
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Gebhart
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D004789:Enzyme Activation; D006162:Guanylate Cyclase / Q000502:physiology*; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D010146:Pain / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D012018:Reflex / Q000187:drug effects*
D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D001120:Arginine; D006162:Guanylate Cyclase