N-Methyl-D-aspartate receptor-mediated signaling in the supraoptic nucleus involves activation of a nitric oxide-dependent pathway.
N-Methyl-D-aspartate (NMDA) microinjection (1 mM, 0.2 microliter) into the hypothalamic supraoptic nucleus (SON) stimulated heart rate in urethane-anaesthetized rats. This effect was inhibited by coinjection of a competitive blocker of NMDA receptors, CPP (20 nmol) or by pretreatment with a sympathetic ganglionic blocker, chlorisondamine chloride (5 mg/kg i.p.), but not by prior hypophysectomy. Furthermore, the cardioexcitatory effect of intra-SON NMDA was inhibited by prior intra-SON injection of a competitive blocker of nitric oxide (NO) synthesis, NG-nitro-L-arginine methyl ester (40 nmol) or a blocker of the soluble guanylate cyclase, Methylene blue (20 nmol), and was mimicked by intra-SON injection of a calcium ionophore, A23187 (10 nmol), which stimulates NO production by raising intracellular free calcium levels. Finally, intra-SON microinjection of a membrane-permeating cGMP analog, 8-bromo-cGMP (20 nmol) stimulated heart rate in urethane-anaesthetized rats. The results point to a functional link between a sympathetically mediated cardiophysiological effect of NMDA receptor stimulation in the SON and activation of the NO/cGMP signal transduction pathway.
Amir
S
S
Department of Psychology, Concordia University, Montreal, Que., Canada.
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002714:Chlorisondamine / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008845:Microinjections; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction; D013495:Supraoptic Nucleus / Q000502:physiology*
D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D000001:Calcimycin; D016202:N-Methylaspartate; D001120:Arginine; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D006152:Cyclic GMP; D002714:Chlorisondamine; D019331:NG-Nitroarginine Methyl Ester