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)

The effects of N-methyl-D-aspartate (NMDA), (+)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), and trans-(+/-)-1-amino-(1S,3R)-cyclopentanedicarboxylic acid (ACPD) on nitric oxide (NO) production in the cerebellum of conscious rats were investigated by measuring the levels of total NO metabolites (nitrite plus nitrate, NOx-) in dialysates obtained by in vivo microdialysis. All glutamate receptor agonists dose-dependently increased NOx- levels. Pharmacological characterization with various glutamate receptor antagonists indicated that the effects of NMDA, AMPA and ACPD are mediated by NMDA, non-NMDA, and L(+)-2-amino-3-phosphonopropionic acid (L(+)-AP-3)-sensitive metabotropic glutamate receptors, respectively. The NO synthase (NOS) inhibitors, including NG-nitro-L-arginine methyl ester (L-NAME), NG-nitro-L-arginine (L-NA), 7-nitroindazole (7-NI), and NG-monomethyl-L-arginine, inhibited NMDA-induced, but not AMPA- or ACPD-induced, increase in NOx- levels. L-Arginine enhanced NMDA-induced, but not AMPA- or ACPD-induced, increase in NOx- levels. Cytochrome P-450 inhibitors, SKF525A and erythromycin, inhibited the effect of NMDA, but not AMPA or ACPD. These results suggest that AMPA and ACPD may induce NO production through a NOS-independent pathway although NMDA receptor-mediated NO production is dependent on NOS activity in the rat cerebellum in vivo.
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PMID:Two pathways of nitric oxide production through glutamate receptors in the rat cerebellum in vivo. 922 Apr 66

Cytochrome P-450 (CYP)-dependent epoxyeicosatrienoic acids (EETs) dilate rat preglomerular microvessels when adenosine(2A) receptors (A(2A)R) are stimulated. As high salt (HS) intake increases epoxygenase activity and adenosine levels, we hypothesized that renal adenosine responses would be greater in HS-fed rats. Male Sprague-Dawley rats were fed either HS (4.0% NaCl) or normal salt (NS; 0.4% NaCl) diet. On day 8, isolated kidneys were perfused with Krebs' buffer containing indomethacin (10 microM) and L-NAME (200 microM) and preconstricted to approximately 150 mmHg with infusion of phenylephrine (10(-7) M). Renal effluents were extracted for analysis of eicosanoids by gas chromatography-mass spectrometry. Bolus injections of the stable adenosine analog 2-chloroadenosine (2-CA; 0.1-10 microg) resulted in dose-dependent dilation; at 10 microg, perfusion pressure (PP) was lowered to a greater extent in the kidneys of HS rats compared with NS rats (-60 +/- 4 vs. -31 +/- 8 mmHg; P < 0.05) and the area of response was increased (27 +/- 6 vs. 9 +/- 4 mm(2); P < 0.05), as was EET release (132 +/- 23 vs. 38 +/- 18 ng; P < 0.05). HS treatment increased A(2A)R and CYP2C23 protein expression. A selective epoxygenase inhibitor, MS-PPOH (12 microM), significantly reduced the response to 2-CA in HS rats; PP, area of response, and EET release decreased by 40, 70, and 81%, respectively, whereas lesser changes were evident in NS kidneys. Thus the greater vasodilator response to 2-CA seen in kidneys obtained from HS-fed rats was mediated by increased EET release. As EETs are renal vasodilator and natriuretic eicosanoids, interactions between adenosine and EETs may contribute to the adaptive response to HS intake.
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PMID:Exaggerated response to adenosine in kidneys from high salt-fed rats: role of epoxyeicosatrienoic acids. 1581 28

Cytochrome P-450 3A (CYP3A) together with its nuclear receptors plays a critical role in drug metabolism. The present study investigated the effects of undernutrition in utero on hepatic mRNA and protein expression of the enzyme CYP3A23/3A1 and nuclear receptors including pregnane X receptor (PXR; NR1I2), constitutive androstane receptor (CAR; NR1I3) and nuclear factor-4alpha (HNF4alpha; HNF4A) in neonatal rats. At gestational day 2, pregnant rats were randomly divided into two groups: nourished (fed ad libitum) and undernourished (50% of nourished group). The pups delivered by nourished rats were designated as the normal-birth-weight group (NBW, n=15) and those delivered by undernourished rats were designated as the low-birth-weight group (LBW, n=15). Hepatic mRNA expression was detected by quantitative real-time PCR and the corresponding protein expression was examined by immunohistochemistry (IHC). Compared with NBW pups, LBW pups tended to have lower mRNA expression levels of CYP3A23/3A1, PXR and CAR but higher levels of HNF4alpha. Only the CAR mRNA expression differences were significant (p<0.05). mRNA expression of CYP3A23/3A1 correlated with that of HNF4alpha in both the LBW(r=0.808, p=0.007) and NBW (r=0.452, p=0.012) groups. CYP3A23/3A1 and CAR protein expression differed between the two groups (CYP3A23/3A1, chi(2)=7.87, p=0.005; CAR, chi(2)=12.069, p=0.001). In conclusion, these findings suggest that undernutrition may influence the mRNA expression of CAR and protein expression of both CYP3A23/3A1 and CAR in neonatal rats. Since CYP3A23/3A1 and CAR are critically involved in drug metabolism, these results may have clinical implications for optimal medication in LBW children.
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PMID:Effects of intrauterine undernutrition on the expression of CYP3A23/3A1, PXR, CAR and HNF4alpha in neonate rats. 1905 92