Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.1.1.1 (alcohol dehydrogenase)
 9,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To define the role of endogenous prostaglandin (PG) synthesis in the vasodilator response to minoxidil (MNX), whole body and regional hemodynamics were measured in conscious, MNX-pretreated dogs before and after the administration of the cyclooxygenase inhibitor indomethacin (INDO). Twenty minutes after an i.v. dose of 2.0 mg/kg, INDO did not affect the reductions in mean arterial pressure and total peripheral resistance achieved with 1.0 mg/kg of MNX i.v. INDO appeared to selectively reverse MNX's vasodilation in the skin and stomach, as vascular resistance in these two tissues increased to pre-MNX levels. Since INDO also exerts a selective vasoconstriction in the skin and stomach of conscious, nonpretreated dogs (Humphrey and Zins, 1983), the fact that skin and stomach resistances were near baseline with this drug combination implies that MNX continues to exert a net vasodilation in these vascular beds. In contrast to INDO's negligible hemodynamic interactions, MNX's vasodilation was nearly completely reversed by continuous i.v. infusions of the direct vasoconstrictor arginine vasopressin (ADH) administered at a mean dose of 35 mU/kg/min. MNX's reversal by ADH was not matched by maximally effective i.v. infusions of the alpha-adrenergic agonist norepinephrine at a mean dose of 0.4 micrograms/kg/min. These results indicate that the sustained peripheral vasodilation seen with MNX in the conscious dog is not dependent upon the synthesis of endogenous, PG-like dilator substances, as defined by concomitant INDO administration.
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PMID:The effects of indomethacin on the systemic and regional vasodilator responses to minoxidil in the conscious dog. 335 78

To define the importance of renal prostaglandins in nephrogenic diabetes insipidus (NDI), diuresis and the urinary excretion of PGE2 and PGF2 alpha were studied in a patient with NDI before and during inhibition of endogenous prostaglandin synthesis with either indomethacin (IND) or acetyl-salicylic acid (ASA). The excretion rates of PGE2 and PGF2 alpha were in the low normal range for the patient's age group, remained unchanged during 6 h of fluid deprivation and were suppressed by IND (150 mg/day), ASA (3 g/day), and by the combination of IND and hydrochlorothiazide (HCT, 50 mg/day). However, whereas IND, HCT, and the combination of IND and HCT reduced diuresis ASA did not. Free water clearance as determined during fluid deprivation remained positive during each phase of therapy. These data fail to demonstrate a direct effect of endogenous ADH on renal prostaglandin synthesis in NDI. The ineffectiveness of ASA to reduce diuresis indicates that indomethacin affects diuresis in NDI by a mechanism other than inhibition of cyclooxygenase.
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PMID:Comparative therapeutic benefit of indomethacin, hydrochlorothiazide, and acetyl-salicylic acid in a patient with nephrogenic diabetes insipidus. 658

Intercellular communication in the liver is a potentially important mechanism for the regulation of hepatic metabolism. Since alcohol (ethanol, ETOH) can interact with both parenchymal and nonparenchymal cells, the present study was performed to assess the possible effects of ETOH on the nonparenchymal cell-to-hepatocyte signal traffic by studying the glycogenolytic and glycolytic response of the perfused rat liver to colloidal carbon, a phagocytic stimulus for Kupffer and sinusoidal endothelial cells. Livers from fed rats were perfused with hemoglobin-free Krebs Ringer bicarbonate buffer containing ETOH (20 mM) or acetaldehyde (1 mM). Twenty minutes after initiating the infusion of ETOH or acetaldehyde, colloidal carbon was infused and the rate of carbon uptake, glucose, lactate and pyruvate output, and oxygen consumption were determined. In control livers, carbon stimulated the output of glucose (60%), lactate (25%), and pyruvate (53%), without affecting the lactate/pyruvate ratio. ETOH, but not acetaldehyde, enhanced the carbon effect on glucose output (38%), but suppressed the increased lactate and pyruvate output (48% and 91% respectively) resulting in a dramatic 10-fold increase in the lactate/pyruvate ratio. By using inhibitors of cyclooxygenase or alcohol dehydrogenase (indomethacin and 4-methylpyrazole, respectively) in the presence of carbon and/or ETOH, we determined that: (1) following carbon stimulation prostaglandins are the likely mediators secreted by nonparenchymal cells that increase carbohydrate output; and (2) the ETOH-induced enhancement of carbon-stimulated glycogenolysis is also mediated by prostaglandins and is not dependent on the oxidative metabolism of ETOH.
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PMID:Ethanol alters the metabolic response of isolated perfused rat liver to a phagocytic stimulus. 845 96

We observed a contractile action of ethanol (20-500 mM) and other alcohols (methanol and propanol, but not butanol) in guinea pig gastric longitudinal (LM) and circular (CM) smooth muscle preparations. The potency order for the alcohols in the LM preparation was: ethanol = propanol > methanol; and in the CM preparation, propanol > ethanol > methanol. Like epidermal growth factor-urogastrone (EGF), the contractile actions of ethanol in the LM and CM preparations required extracellular calcium and were blocked by the tyrosine kinase inhibitors, genistein and tyrphostin-47 (AG213). The tyrosine phosphatase inhibitor, pervanadate, potentiated the contractile action of ethanol in the LM preparation. Ethanol-induced contractions in both preparations were not affected by 4-methyl pyrazole, an inhibitor of alcohol dehydrogenase, and were unaffected by tetrodotoxin, atropine, prazosine or yohimbine. In the LM preparation, like EGF, the contractile action of ethanol was blocked by the cyclooxygenase inhibitor, indomethacin, and the diacylglycerol lipase inhibitor, U57,908; in the CM preparation, contractions caused by ethanol and EGF were still observed in the presence of these two inhibitors. Contractions caused by ethanol and EGF in the LM preparation were not affected by the epoxygenase inhibitor, ketoconazole; the lipoxygenase inhibitor, nordihydroguaiaretic acid; or the phospholipase A2 inhibitor, mepacrine. In contrast, in the LM preparation, EGF-induced contractions were attentuated by the EGF receptor-kinase inhibitor, PD153035; the MAP-kinase-kinase (MEK) inhibitor, PD98059; the kinase C inhibitor, GF109203X; and the phosphatidylinositol 3'-kinase inhibitors, Wortmannin and LY294002; whereas ethanol-induced contractions were unaffected by these inhibitors. Both ethanol and EGF caused small increases in the phosphotyrosyl protein content of the gastric tissue. We conclude that ethanol causes its contractile effects in the distinct gastric LM and CM preparations independent of nerve-released agonists and via a tyrosine kinase inhibitor-sensitive signal pathway that is in many respects similar to, but distinct from the one activated by EGF.
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PMID:Contractile action of ethanol in guinea pig gastric smooth muscle: inhibition by tyrosine kinase inhibitors and comparison with the contractile action of epidermal growth factor-urogastrone. 922 91

Pairs of forward and reverse primers and TaqMan probes specific to each of 52 human phase I metabolizing enzymes (alcohol dehydrogenase, aldehyde dehydrogenase, aldehyde oxidase, dihydropyrimidine dehydrogenase, epoxide hydrolase, esterase, flavin-containing monooxygenase, monoamine oxidase, prostaglandin endoperoxide synthase, quinone oxidoreductase, and xanthene dehydrogenase) and 48 human phase II metabolizing enzymes (acetyltransferase, acyl-CoA:amino acid N-acyltransferase, UDP-glucuronosyltransferase, glutathione S-transferase, methyltransferase, and sulfotransferase) were prepared. The mRNA expression level of each target enzyme was analyzed in total RNA from single and pooled specimens of various human tissues (adrenal gland, bone marrow, brain, colon, heart, kidney, liver, lung, pancreas, peripheral leukocytes, placenta, prostate, salivary gland, skeletal muscle, small intestine, spinal cord, spleen, stomach, testis, thymus, thyroid gland, trachea, and uterus) by real-time reverse transcription PCR using an ABI PRISM 7700 Sequence Detection System. Further, individual differences in the mRNA expression of representative human phase I and II metabolizing enzymes in the liver were also evaluated. The mRNA expression profiles of the above phase I and phase II metabolizing enzymes in 23 different human tissues were used to identify the tissues exhibiting high transcriptional activity for these enzymes. These results are expected to be valuable in establishing drug metabolism-mediated screening systems for new chemical entities in new drug development and in research concerning the clinical diagnosis of disease.
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PMID:Tissue-specific mRNA expression profiles of human phase I metabolizing enzymes except for cytochrome P450 and phase II metabolizing enzymes. 1707 89