Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the effects of age and NG-nitro-L-arginine methyl ester (L-NAME) on glutamate receptor systems and immunophilin in Fischer rat brain using receptor autoradiography. [3H]MK-801, [3H]glycine, sodium-dependent [3H]D-aspartate and [3H]FK-506 were used to label N-methyl-D-aspartate (NMDA) receptors, glycine receptors, excitatory amino acid transport sites and FK-506 binding proteins (FKBP), respectively. [3H]Glycine and sodium-dependent [3H]D-aspartate binding significantly reduced in the cerebral cortex, striatum, hippocampus, thalamus, substantia nigra and cerebellum of aged (24-month-old) rats in comparison with adult (6-month-old) animals. In contrast, [3H]MK-801 and [3H]FK-506 binding showed no significant changes in most brain regions of aged rats. Intraperitoneal chronic treatment with L-NAME (5 mg/kg, once a day for 4 weeks) showed no conspicuous changes in these binding sites in most brain areas of aged rats. In the cerebellum, however, this treatment showed a significant change in both [3H]MK-801 and sodium-dependent [3H]D-aspartate binding in aged rats. These results demonstrate that glycine receptors and excitatory amino acid transport sites are more susceptible to aging processes than NMDA receptors and FKBP. Furthermore, our findings may suggest a possible role of nitric oxide in the regulation of cerebellum during aging processes.
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PMID:Effect of NG-nitro-L-arginine on age-related changes of glutamate receptor systems and immunophilin in rats. 938 86

FK506 is an immunophilin-binding ligand that inhibits calcineurin and decreases nitric oxide (NO) production in the nervous tissues. We examined the effects in mice of systemic treatment with FK506 on the induction and expression of morphine (s.c.) tolerance and dependence and compared them with the effects of the non-specific NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), and specific inducible NO synthase inhibitor, aminoguanidine. FK506 (0.5-10 mg/kg, s.c.) exerted inhibitory effects on both development and expression of tolerance to morphine-induced antinociception. FK506 also significantly decreased the expression of morphine dependence, as assessed by naloxone-precipitated (2 mg/kg, i.p.) withdrawal syndrome, but a similar effect was not found for the development of morphine dependence. A similar pattern of effects was observed with L-NAME (3-20 mg/kg, i.p.), while aminoguanidine (50-100 mg/kg, i.p.) did not alter tolerance or dependence. Examining the possible interaction between their inhibitory effects on tolerance and dependence, we combined the subeffective doses of FK506 (0.5 or 1 mg/kg) with L-NAME (3 mg/kg) or aminoguanidine (100 mg/kg). The combination of FK506 with L-NAME, but not with aminoguanidine, significantly decreased the development and expression of tolerance and expression of dependence. These data show the effectiveness of FK506 on morphine tolerance and dependence and suggest an additive effect between FK506 and the inhibition of constitutive NO synthesis in this regard.
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PMID:The effects of FK506 on the development and expression of morphine tolerance and dependence in mice. 1265 72

It has been suggested that immunophilin ligands such as cyclosporine and FK-506 (tacrolimus) affect the survival of ischemic tissues. Our objective was to show an acute effect of local cyclosporin-A (CsA) and FK-506 on ischemic protection in a random-pattern skin-flap model in rats and investigate the effect of nitric oxide (NO) pathways as a modulator of protection of these agents. Ninety male Sprague-Dawley rats were randomly assigned to treatment groups. Bipedicled dorsal flaps (2 x 8 cm) were elevated at midline. Prior to cutting the cranial pedicle to induce permanent ischemia, pharmacologic preconditioning groups received local injection of CsA (0.3, 1, or 3 nmol/flap) or FK-506 (0.01, 0.03, or 0.1 pmol/flap), and the ischemic preconditioning (IPC) group underwent temporary clamping of the cranial pedicle. At the seventh day postoperatively, the survival of the flaps was measured. In other groups, nitric oxide synthase inhibitor N omega-nitro-l-arginine methyl ester hydrochloride (L-NAME) was administered with effective CsA and FK-506, and ischemic preconditioning. Nitric oxide precursor L-arginine doses were also studied, and a systemic subeffective dose (100 mg/kg) was coadministered with subeffective CsA and FK-506. Significant increase in flap survival was obtained with CsA (1 nmol/flap), FK-506 (0.1 pmol/flap), and IPC. These protections were abolished by systemic administration of L-NAME (10 mg/kg). Coadministration of subeffective doses of CsA (0.3 nmol/flap) and FK-506 (0.03 pmol/flap), with subeffective systemic l-arginine, significantly improved flap survival.Pharmacologic preconditioning with local, single, low doses of CsA or FK-506 is shown to be even more effective than IPC. Administration of the NOS substrate l-arginine potentiates these effects.
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PMID:Pharmacologic preconditioning of random-pattern skin flap in rats using local cyclosporine and FK-506: interaction with nitric oxide system. 1790 37