Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently, two N-terminal splice variants of the metabotropic receptor for GABA (gamma-amino-butyric acid) were cloned. Here, we describe an antiserum that recognizes the two receptor variants. We demonstrate that these proteins are identical with GABAB receptors that are photoaffinity labeled with [125I]CGP71872 in rat brain. The C-terminal epitopes recognized by the antiserum are conserved in several vertebrate species but not in chicken. No hints for the existence of additional closely related receptor subtypes or variants are found in double-labeling experiments with antibody and photoaffinity ligand. Western blot analysis reveals widespread expression of the GABABR1 receptor proteins in rat brain with the highest level of expression at early postnatal stages. The binding affinity of the GABAB receptor agonist L-baclofen at native R1a and R1b variants is similar. In early postnatal development the affinity at R1a and R1b is 10-fold lower than in adult brain and gradually increases with aging.
Mol Cell Neurosci 1998 Sep
PMID:Developmental changes of agonist affinity at GABABR1 receptor variants in rat brain. 977 Mar 40

The evolution of chordate glutamic acid decarboxylase (GAD; EC 4.1.1.15), a key enzyme in the central nervous system synthesizing the neurotransmitter gamma-amino-butyric acid (GABA) from glutamate, was studied. Prior to this study, molecular data of GAD had been restricted to mammals, which express two distinct forms, GAD65 and GAD67. These are the products of separate genes and probably are derived from a common ancestral GAD following gene duplication at some point during vertebrate evolution. To enable a comprehensive phylogenetic analysis, molecular information of GAD forms in other vertebrate classes was essential. By reverse transcriptase-polymerase chain reaction (RT-PCR), partial nucleotide sequences of GAD were cloned from brains of zebra finch (Taeniopygia guttata), turtle (Trachemys scripta), goldfish (Carassius auratus), zebrafish (Danio rerio), and armoured grenadier (Coryphaenoides (Nematonurus) armatus, a deep-sea fish), and from the cerebral ganglion plus neural gland of Ciona intestinalis, a protochordate. Whereas GAD65 and GAD67 homologs were expressed in birds, reptiles, and fish, only a single GAD cDNA with equal similarities to both vertebrate GAD forms was found in the protochordate. This indicates that the duplication of the vertebrate GAD gene occurred between 400 and 560 million years ago. For both GAD65 and GAD67, the generated phylogenetic tree followed the general tree topology for the major vertebrate classes. In turtle, an alternative spliced form of GAD65, putatively encoding a truncated, nonactive GAD, was found. Furthermore, a third GAD form, which is equally divergent from both GAD65 and GAD67, is expressed in C. (N.) armatus. This third form might have originated from an ancient genome duplication specific to modern ray-finned fishes.
Mol Biol Evol 1999 Mar
PMID:Multiplicity of glutamic acid decarboxylases (GAD) in vertebrates: molecular phylogeny and evidence for a new GAD paralog. 1033 Dec 65

The lectin concanavalin A (ConA) when applied to the olfactory mucosa (OM) of frog and rat, is reported to partially inhibit electro-olfactogram (EOG) responses to fatty acid odours. Control odours like isoamyl acetate were not affected. We have now studied in the frog whether this treatment affects the corresponding olfactory bulb (OB) response. The OB surface was impregnated with a voltage-sensitive dye (RH 414). Spatial and temporal patterns of odour response were measured by changes in dye fluorescence that occur when OB neurons fire. The apparatus, consisted of an epi-fluorescent microscope coupled to a 64 x 64 pixel CCD photodetection camera. This allowed imaging over an 0.9 mm2 area of the OB glomerular layer to high resolution. When the frog OM was bathed with 5 mg ml(-1) ConA in Ringer's solution, the n-butyric acid odour response in the OB largely disappeared while the isoamyl acetate response did not change. When this experiment was repeated in the presence of 20 mM methyl alpha-D mannopyranoside (a ConA inhibitor), ConA failed to inhibit the n-butyric acid response. Moreover the ConA effect was partially reversible. A Ringer's wash of the OM after ConA treatment, partially restored the OB response to n-butyric acid. Thus the olfactory bulb results seem compatible with the EOG results and reinforce the notion that ConA selectively prevents n-butyric acid sensitive olfactory receptor neurons from firing. Chemical modification of the OM and their effect on OB response patterns may provide a useful approach to investigate olfactory quality coding.
Cell Mol Biol (Noisy-le-grand) 1999 May
PMID:Selective and reversible blockage of a fatty acid odour response in the olfactory bulb of the frog (Rana temporaria). 1038 90

Phospholipids are important constituents of biomembrane components and are supposed to function as enzyme activators or precursors of bioactive substances. Our earlier work has shown an increased esterification of neutral lipids of HT-29 cells during butyrate-induced differentiation (M. Madesh, O. Benard, K.A. Balasubramanian, Butyrate-induced alteration in lipid composition of human colon cell line HT-29, Biochem. Mol. Biol. Int. 38 (1996) 659-664). In this report we show that there is an increase in phospholipase D (PLD) activity during butyrate-induced differentiation of HT-29 cells as indicated by the formation of phosphatidic acid (PA). When the control and butyrate-treated cell homogenates were incubated in vitro with 1 mM Ca2+, the increase in PA formation was higher than in butyrate-treated cells. This PA was formed due to PLD activity that was confirmed by the generation of phosphatidylethanol by in vitro incubation of HT-29 cell homogenates in the presence of ethanol. The formation of PA was associated with a decrease in phosphatidylcholine (PC) and phosphatidylethanolamine (PE). This study has shown an increase in PLD activity associated with the differentiation of HT-29 cells.
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PMID:Increased phospholipase D activity in butyrate-induced differentiation of HT-29 cells. 1039 65

The Ah receptor (AhR) is a ligand-dependent transcription factor that mediates biological and toxicological actions of halogenated aromatic hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-p-dioxin. Although much is known about the biochemical and molecular mechanisms of AhR action, little is known about the factors and events that control expression of the AhR gene itself. The 5'-flanking region of the murine AhR gene was characterized and deletion analysis demonstrated that regulatory elements necessary for full constitutive promoter activity are contained within a fragment encompassing -184 to +380 of the AhR gene. The murine AhR gene promoter is a GC-rich, TATA-less promoter that which contains at least five putative Spl-like binding sites. Transient transfection experiments not only identified a region between -1431 and -721 that represses constitutive promoter activity by 2- to 3-fold, but also demonstrate that basal AhR promoter activity occurs in a cell- and species-specific manner. n-Butyrate, a nonspecific histone deacetylase inhibitor, increased AhR promoter activity 8-fold, suggesting a role for histone acetylation in AhR gene promoter activity. Overall, this study defines upstream regulatory regions important for constitutive AhR gene expression and identifies a novel activator of AhR gene expression.
J Biochem Mol Toxicol 2000
PMID:Analysis of the murine AhR gene promoter. 1056 Oct 76

Nutrient interactions during intestinal digestion has been established in animals. The present study investigated the effect of different nutrients on intestinal dipeptidase, tripeptidase, carboxypeptidase (EC 3.4.12.-) and aminopeptidase N (ApN) (EC 3.4.11.2) activities in human fetuses and children. The effect of nutrients on isolated porcine kidney ApN was also studied. Sucrose, lactose and tributyrin had no effect on di-, tri-, and carboxypeptidase activities of mucosal homogenates, but tributyrin significantly (20-50%) inhibited both fetal and postnatal ApN activity in the small intestine and colon. The pH-independent inhibition of ApN is specific for tributyrin and to the product of its hydrolysis, butyric acid. Glycerol, triolein, and natural oils did not affect ApN activity. The inhibition of ApN by tributyrin was dose and time dependent and occurred in enterocyte brush border membranes as well as in the purified enzyme from porcine kidney. The kinetics of the purified ApN showed that the tributyrin effect is primarily competitive and associated mainly with an increase in K(m). These observations demonstrate the possibility of intestinal and kidney ApN regulation by lipids and products of their hydrolysis. We speculate that nutrient interactions arose quite early in the evolution and represent a mechanism for the regulation of food digestion.
Comp Biochem Physiol A Mol Integr Physiol 1999 Oct
PMID:Regulation of intestinal peptidases by nutrients in human fetuses and children. 1062 59

The role of melatonin in the regulation of human reproduction remains unclear. In the present study, we examined the influence of exogenous melatonin on pulsatile luteinizing hormone (LH), diurnal rhythm of testosterone, and endogenous melatonin profile in six healthy young adult males. To test the hypothesis that the effect of melatonin on LH or testosterone secretory patterns may be mediated through the benzodiazepine-(BNZ) gamma-amino-butyric acid (GABA) receptor complex, a benzodiazepine receptor antagonist (Flumazenil) was administered. The study design comprised four 10-h (4:00 PM-2:00 AM) testing periods. During each experimental period, subjects were given an oral dose of placebo, or 3 mg melatonin or 10 mg flumazenil, at 5:00 PM, in a randomized, double-blind, partially repeated Latin square design in the following combinations: placebo-placebo, placebo-melatonin, flumazenil-placebo, and flumazenil-melatonin. The following day, serum samples were obtained every 20 min between 4:00 PM and 2:00 AM in a controlled light-dark environment for the determination of LH and melatonin levels. Serum testosterone concentrations were determined every 20 min between 7:00 and 8:00 AM and 7:00 and 8:00 PM. A significant decrease in mean serum LH levels (p < 0.02) was observed in the melatonin-treated groups as compared with placebo-flumazenil groups. There was no change in LH pulse frequency, testosterone levels, or in melatonin onset time and amplitude. No additional effect of flumazenil on LH or testosterone levels was observed. These data indicate that an evening melatonin administration decreases the next-day LH secretion in normal adult males without altering testosterone levels or the endogenous nocturnal melatonin secretory pattern. This effect of melatonin is not mediated through the benzodiazepine-GABA receptor complex.
J Mol Neurosci 1999 Feb
PMID:Melatonin administered in the afternoon decreases next-day luteinizing hormone levels in men: lack of antagonism by flumazenil. 1063 72

A pilot phase II open study on 12 patients with thalassemia intermedia (7 men, 5 women; age 31 +/- 2.0 years SE) treated with oral isobutyramide, a derivative of butyric acid (150 mg/kg body wt/day), was performed in order to evaluate the effect of this compound in stimulating hemoglobin F (HbF) production. No patient underwent blood transfusion in the 1-year time frame prior to the study. Nine patients were splenectomized. Safety was monitored by clinical and laboratory tests. Efficacy was assessed in terms of the non-alpha/alpha globin chain biosynthetic ratio and the percentage increase of HbF. The study design consisted of a screening phase, a treatment phase of 28 days, and a posttreatment follow-up of 28 days. All patients completed the study. Compliance to treatment was 100%. No drug-related adverse event was recorded. We observed little or no increase in the non-alpha/alpha ratio in the majority of patients. Six patients showed a percentage increase of HbF at the end of treatment and in 5 of those 6 further increases at the end of the follow-up period were observed. The change in percentage of HbF over time was close to significance both in the treatment period (P = 0. 06) and in the follow-up period (P = 0.08). These results indicate that butyrate derivatives can stimulate fetal hemoglobin in patients with intermediate thalassemia. Testing of the effects of different schedules of administration of isobutyramide will be required in order to determine the optimal use of this compound in the treatment of the beta-thalassemia syndromes.
Blood Cells Mol Dis 2000 Feb
PMID:Oral isobutyramide therapy in patients with thalassemia intermedia: results of a phase II open study. 1077 82

The study of fluorescence energy transfer from the phenyl groups of the micellar triton X-100 (TX-100) to solubilised 1-pyrene butyric acid (PBA) has been carried out. Through the analysis of the donor fluorescence quenching energy transfer efficiency has been determined. The observed donor-acceptor separation suggests that pyrene molecules are distributed uniformly in the micellar core.
Spectrochim Acta A Mol Biomol Spectrosc 2000 Mar
PMID:Energy transfer in triton-X 100 micelles: a fluorescence study. 1079 53

Arterial injury-induced vascular smooth muscle cell (VSMC) proliferation in intima is the important etiologic factor in vascular proliferative disorders such as atherosclerosis, hypertension and restenosis after balloon angioplasty. Butyrate, a naturally occurring short chain fatty acid, is produced by bacterial fermentation of dietary fiber and by mammary glands of certain mammals. Studies have shown that butyrate at millimolar concentrations, which are physiological, induces growth arrest, differentiation and apoptosis. We examined the effect of physiological concentrations of butyrate on rat VSMC proliferation and proliferation-induced PCNA expression to determine anti-atherogenic potential of butyrate. Butyrate concentrations, closer to physiological range, exhibited antiproliferative effects on both serum-induced proliferation of serum-starved quiescent VSMCs and actively proliferating non-confluent VSMCs. Treatment of serum-starved quiescent VSMCs with 1-8 mmol/l concentration of butyrate caused a concentration-dependent decrease in serum-induced VSMC proliferation and cell proliferation-associated increase in total cellular proteins and RNA levels. Similarly, exposure of actively growing VSMCs to 5 mmol/l butyrate resulted in the inhibition of cell proliferation and proliferation-induced increase in cellular proteins and RNA levels. Furthermore, cellular morphology was significantly altered. Analysis of cell cycle regulatory proteins indicated that levels of PCNA, an excellent marker for cell proliferation, was significantly altered by butyrate both in actively proliferating and serum-induced quiescent VSMCs. These observations suggest that butyrate exhibits potential antiatherogenic capability by inhibiting VSMC proliferation and proliferation-associated increase in PCNA expression and thus merits further investigations regarding therapeutic significance of butyrate in vascular proliferative disorders.
Mol Cell Biochem 2000 Feb
PMID:Butyrate inhibits proliferation-induced proliferating cell nuclear antigen expression (PCNA) in rat vascular smooth muscle cells. 1082 33


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