Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A dose of N-methyl-D-aspartic acid (NMDA, 50 ng) that induces penile erection and yawning when injected into the paraventricular nucleus of the hypothalamus, increased the concentration of NO2- from 1.10 +/- 0.28 microM to 7.32 +/- 1.12 microM and of NO3 from 4.96 +/- 0.69 microM to 10.5 +/- 1.61 microM in the paraventricular dialysate obtained from male rats by in vivo microdialysis. NO2- concentration was not increased by (+/-)-alpha-(amino)-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA, 100 ng) or by trans-(+/-)-1-amino-1,3-cyclopentanedicarboxylic acid (ACPD) (100 ng), which were unable to induce these behavioral responses. N-Methyl-D-aspartic acid effect on NO2- concentration, penile erection and yawning was prevented by dizolcipine (MK-801) (10-100 ng) or by the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (20 microg), but not by the oxytocin receptor antagonist [d(CH2)5,Tyr(Me)2,Orn8]vasotocin (100 ng), or by the guanylate cyclase inhibitor methylene blue (20 microg) given in the paraventricular nucleus 15 min before N-methyl-D-aspartic acid or by the dopamine receptor antagonist haloperidol (0.5 mg/kg) given intraperitoneally 30 min before N-methyl-D-aspartic acid. In contrast, the nitric oxide scavenger hemoglobin (20 microg) given in the paraventricular nucleus prevented N-methyl-D-aspartic acid-induced NO2- concentration increase, but was unable to prevent penile erection and yawning. The results suggest that N-methyl-D-aspartic acid induces penile erection and yawning by increasing nitric oxide synthase activity in the paraventricular nucleus of the hypothalamus, possibly in the cell bodies of oxytocinergic neurons projecting to extra-hypothalamic brain areas and mediating these behavioral responses.
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PMID:N-methyl-D-aspartic acid-induced penile erection and yawning: role of hypothalamic paraventricular nitric oxide. 921 92

In this study, we analyzed the mechanism of selective motor neuronal death, a characteristic of amyotrophic lateral sclerosis, using embryonic rat spinal cord culture. When dissociated cultures were exposed to low-level glutamate (Glu) coadministered with the Glu transporter inhibitor L-trans-pyrrolidine-2,4-decarboxylate (PDC) for 24 hours, motor neurons were selectively injured through N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)/kainate receptors. Nitric oxide synthase (NOS) inhibitors attenuated this toxicity, and long-acting nitric oxide (NO) donors damaged motor neurons selectively. Nonmotor neurons survived after exposure to low-dose Glu/PDC, but Glu-induced toxicity was potentiated by coadministration of an NO-dependent guanylyl cyclase inhibitor. In addition, 8-bromo-cyclic GMP, a soluble cyclic GMP analogue, rescued nonmotor neurons, but not motor neurons, exposed to high-dose Glu/PDC. Twenty-four hours' incubation with PDC elevated the number of neuronal NOS-immunoreactive neurons by about twofold compared with controls, and a double-staining study, using the motor neuron marker SMI32, revealed that most of them were nonmotor neurons. These findings suggest that selective motor neuronal death caused by chronic low-level exposure to Glu is mediated by the formation of NO in nonmotor neurons, which inversely protects nonmotor neurons through the guanylyl cyclase-cyclic GMP cascade. Induction of neuronal NOS in nonmotor neurons might enhance both the toxicity of motor neurons and the protection of nonmotor neurons, which could explain the pathology of amyotrophic lateral sclerosis.
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PMID:Mechanism of selective motor neuronal death after exposure of spinal cord to glutamate: involvement of glutamate-induced nitric oxide in motor neuron toxicity and nonmotor neuron protection. 981 36

In pentobarbital-anesthetized rats, intrathecal injection of noradrenaline (NA; 6, 18 and 60 nmol) induced a dose-dependent increase in the mean blood pressure. The pressor response to NA (18 nmol) was blocked by pretreatment with the selective antagonist for N-methyl-D-aspartic acid (NMDA) receptors, 2-amino-5-phosphonovaleric acid (30 nmol), but not by pretreatment with the selective antagonist for (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid/kainate receptors, 6,7-dinitroquinoxaline-2,3-dione (50 nmol). The pressor effect of NA was reduced after pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME, 1 micromol). The effect of L-NAME on the pressor response to NA was reverted by the precursor of nitric oxide (NO), L-arginine (5 micromol). The hypertension induced by NA was also reduced by the guanylate cyclase inhibitor methylene blue (0.3 micromol). These results suggest that spinal NMDA receptors and spinal NO are involved in the pressor response to NA.
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PMID:Participation of nitric oxide and N-methyl-D-aspartic acid receptors in the pressor response to intrathecal injected noradrenaline at the spinal cord of the rat. 1216 93

We sought to test the hypothesis that cardiovascular responses to activation of ionotropic, but not metabotropic, glutamate receptors in the nucleus tractus solitarii (NTS) depend on soluble guanylate cyclase (sGC) and that inhibition of sGC would attenuate baroreflex responses to changes in arterial pressure. In adult male Sprague-Dawley rats anesthetized with chloralose, the ionotropic receptor agonists N-methyl-d-aspartate (NMDA) and dl-alpha-amino-3-hydroxy-5-methylisoxazole-propionic acid (AMPA) and the metabotropic receptor agonist trans-dl-amino-1,3-cyclopentane-dicarboxylic acid (ACPD) were microinjected into the NTS before and after microinjection of sGC inhibitors at the same site. Inhibition of sGC produced significant dose-dependent attenuation of cardiovascular responses to NMDA but did not alter responses produced by injection of AMPA or ACPD. Bilateral inhibition of sGC did not alter arterial pressure, nor did it attenuate baroreflex responses to pharmacologically induced changes in arterial pressure. This study links sGC with NMDA, but not AMPA or metabotropic, receptors in cardiovascular signal transduction through NTS.
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PMID:NMDA receptors in nucleus tractus solitarii are linked to soluble guanylate cyclase. 1502 Mar 5