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Query: UNIPROT:P06889 (Mol)
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In experiments with reaction centers (RC) preparations of Rps. sphaeroides, strain 1760-1, pH of the suspension medium was found to change under continuous light excitation. The concentration of hydrogen ions starts to decrease fastly (t1/2 = 2--4 s) after the light is on, whereupon it increases slowly, to a steady-state level, within t1/2 = 5--7 min. During the fast phase 0.3 microM H+/1 microM of RC are absorbed and 7--8 microM H+/1 microM of RC are released under the slow phase. The fast phase is suppressed by ortho-phenantroline (10 mM)--an inhibitor of electron transfer from the primary (Fe-quinone complex) to the secondary (quinone) electron acceptors. Glutaraldehyde which is known to modify a protein structure of the RC inhibits the slow phase. The obtained data suggest that fast light-induced pH changes are due to a H+ uptake by the secondary quinoid anion-radical products; slow pH changes are ascribed to structural changes within the RC complex, which lead to a pK shift and/or changes in the amount of dissociating groups on the protein interfacial surface. The conclusion was supported by an observation of light-induced changes in buffer capacity of an RC suspension and by a light-induced increase in the amount of SH-groups titrated by 5.5-dithio-bis(2 nitro)-benzoic acid. The role of conformational dynamics of photoactive pigment--protein complexes in the functions of the RC is discussed.
Mol Biol (Mosk)
PMID:[Light-induced changes in pH and buffer capacity in reaction center preparations of Rhodopseudomonas spheroides]. 701 84

Whole-cell patch-clamp recordings of membrane currents were performed in combination with measurements of mediator secretion from mucosal-type mast cells (rat basophilic leukemia cells, subline 2H3), to determine the involvement of membrane conductances induced upon depletion of intracellular Ca2+ stores. In patch-clamp experiments, ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid-induced depletion of internal Ca2+ stores led to activation of two distinct membrane conductances, a Ca2+ current and a Cl- current. The Ca2+ current was blocked by 100 microM La3+, which did not affect the Cl- current. In contrast, 500 microM 4,4'-diisothiocyanato-2,2'-disulfonic acid produced selective blocked of the Cl- current. Remarkably, the Cl- channel blockers 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), niflumic acid, and N-phenylanthranilic acid (NPAA) inhibited not only the Cl- current but also the Ca2+ current. IC50 values for the blockade of the Ca2+ inward current by NPPB, niflumic acid, and NPAA were determined to be 23, 150, and 190 microM, respectively. In secretion experiments, thapsigargin-induced depletion of internal Ca2+ stores stimulated serotonin release, which was found to be strictly dependent on extracellular Ca2+. In the presence of 100 microM La3+ secretion was almost completely inhibited. In contrast, only 50% of secretion was suppressed by 500 microM 4,4'-diisothiocyanato-2,2'-disulfonic acid, which fully blocked the Cl- current without affecting Ca2+ influx, as monitored by electrophysiological experiments. The other Cl- channel blockers produced a very different pattern for the inhibitory dose dependence of secretion, with IC50 values for NPPB, niflumic acid, and NPAA of 23, 60, and 180 microM, respectively. Taken together, these findings suggest that Ca2+ store depletion leads to concomitant activation of Cl- and Ca2+ currents. Blockade of the latter is apparently an additional mode of action for diarylaminocarboxylate-type Cl- channel blockers inhibiting mast cell secretory responses.
Mol Pharmacol 1995 May
PMID:Blockade of capacitive Ca2+ influx by Cl- channel blockers inhibits secretion from rat mucosal-type mast cells. 774 67

This report describes chloride and iodide effluxes across the basolateral membrane of porcine thyroid follicles reconstituted in culture. Basolateral chloride efflux is activated by thyrotropin (TSH). TSH (10 mU/ml) induces a twofold increase in the initial rate of chloride efflux. Forskolin (FSK, 5 microM) which increases intracellular cAMP also stimulates the initial rate of chloride efflux 3.5-fold, whereas an increase in the free cytosolic Ca2+ with the ionophore A23187 or thapsigargin, fails to mimic the TSH effect. The chloride channel blocker 5-nitro-2(3-phenylpropylamino)benzoic acid (NPPB) dose dependently inhibits chloride efflux rates with the maximal and half maximal effects observed for 100 microM and 30 microM, respectively. Basolateral chloride efflux rates are also inhibited in the presence of the organic anion transporter blocker probenecid (5 mM) or the Cl-/HCO3- exchanger blocker 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS, 250 microM), respectively, by 60% and 40%, whereas it is not affected by ClO4 (100 microM). The initial rate of iodide efflux is weakly activated (1.4-fold) by TSH (10 mU/ml). TSH effect could be reproduced by agents known to activate Ca(2+)-dependent processes as A23187, ionomycin (1 microM), phorbol 12-myristate 13-acetate (TPA, 0.1 microM) and epidermal growth factor (EGF, 0.1 microM) which increase the initial rate of iodide efflux from 1.2- to 1.8-fold, whereas FSK is without effect. The chloride channel blocker NPPB (500 microM) is required to significantly inhibit the initial rate of iodide efflux by 30%. The initial rate of iodide efflux is also reduced by 30% in the presence of SITS (250 microM) or probenecid (5 mM) whereas it is activated by ClO4 (100 microM). We conclude that basolateral chloride and iodide effluxes are both regulated by TSH, using two different transduction pathways. Chloride efflux regulation may involve a cAMP transduction signal, whereas the regulation of iodide efflux may involve a Ca2+ signal. Furthermore, as the sensitivities of chloride and iodide effluxes for the anion transporter blockers (especially NPPB) are different, it seems likely that chloride and iodide use two different transport pathways.
Mol Cell Endocrinol 1994 Dec
PMID:Thyrotropin regulation of basolateral Cl- and I- effluxes in thyroid follicles in culture. 789 8

LF 7-0156 (2-[[[2-butyl-1-[(4-carboxyphenyl)methyl]-1H-imidazol- 5-yl]methyl]amino]benzoic acid) is a nonpeptide angiotensin II receptor antagonist selective for the type 1 angiotensin receptor. In rabbit aortic rings, LF 7-0156 competitively antagonized angiotensin II-induced contractile responses, with a pA2 value of 8.44. The synthesis of the radiolabeled compound [3H]LF 7-0156 has allowed direct binding studies with several membrane or cell preparations. Consistent with competition experiments, the binding of [3H]LF 7-0156 to purified rat liver membranes was characterized by a Kd value of 12.6 nM and very low pseudospecific or nonspecific binding; this latter characteristic confers to this compound an advantage over the structurally different compound [3H]DuP 753, which is the only commercially available nonpeptide radioligand. [3H]LF 7-0156 also bound to the type 1A angiotensin receptor expressed in Chinese hamster ovary cells, with high affinity (Kd = 3.5 nM) and a total absence of nonspecific binding. Functional antagonism in this cell system was assessed by the ability of LF 7-0156 to reverse angiotensin II-induced inositol phosphate production. These properties make [3H]LF 7-0156 an interesting pharmacological tool and should allow future evaluation of recognition of the nonpeptide ligand by mutated receptors expressed in Chinese hamster ovary cells; it will facilitate the analysis of possible differences in receptor amino acids involved in the binding of peptide and nonpeptide ligands, as well as the extent of spatial overlap between several nonpeptide antagonists displaying different structural properties.
Mol Pharmacol 1994 Oct
PMID:Properties of [3H]LF 7-0156, a new nonpeptide antagonist radioligand for the type 1 angiotensin II receptor. 796 48

The inhibition mechanism of the dimeric human placenta glutathione transferase (GST P1-1) by the antibiotic p-carboxyphenylazoxycyanide (calvatic acid) has been investigated at pH 7.0 and 30.0 degrees C. Experiments performed at different calvatic acid/GST P1-1 molar ratios indicate that one mole of calvatic acid inactivates one mole of the homodimeric enzyme molecule, containing two catalytically equivalent active sites. The apparent second order rate constant for GST P1-1 inactivation is 2.4 +/- 0.3 M-1 s-1. The recovery of all the 5,5'-dithio-bis(2-nitro-benzoic acid)-titratable thiol groups as well as the original catalytic activity of GST P1-1 after treatment of the inhibited enzyme with dithiothreitol indicates that two disulfide bridges per dimer, likely between Cys47 and Cys101, have been formed during the reaction with calvatic acid. To the best of the authors knowledge, calvatic acid represents a unique case of enzyme inhibitor acting also throughout its reaction product(s).
Biochem Mol Biol Int 1994 Apr
PMID:Inhibition of human placenta glutathione transferase P1-1 by calvatic acid. 806 31

Considering the link between plasma high-density lipoprotein (HDL) cholesterol levels and a protective effect against coronary artery disease as well as the suggested beneficial effects of retinoids on the production of the major HDL apolipoprotein (apo), apo A-I, the goal of this study was to analyze the influence of retinoids on the expression of apo A-II, the other major HDL protein. Retinoic acid (RA) derivatives have a direct effect on hepatic apo A-II production, since all-trans (at) RA induces apo A-II mRNA levels and apo A-II secretion in primary cultures of human hepatocytes. In the HepG2 human hepatoblastoma cell line, both at-RA and 9-cis RA as well as the retinoid X receptor (RXR)-specific agonist LGD 1069, but not the RA receptor (RAR) agonist ethyl-p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-l-pro penyl]-benzoic acid (TTNPB), induce apo A-II mRNA levels. Transient-transfection experiments with a reporter construct driven by the human apo A-II gene promoter indicated that 9-cis RA and at-RA, as well as the RXR agonists LGD 1069 and LG 100268, induced apo A-II gene expression at the transcriptional level. Only minimal effects of the RAR agonist TTNPB were observed on the apo A-II promoter reporter construct. Unilateral deletions and site-directed mutagenesis identified the J site of the apo A-II promoter mediating the responsiveness to RA. This element contains two imperfect half-sites spaced by 1 oligonucleotide. Cotransfection assays in combination with the use of RXR or RAR agonists showed that RXR but not RAR transactivates the apo A-II promoter through this element. By contrast, RAR inhibits the inductive effects of RXR on the apo A-II J site in a dose-dependent fashion. Gel retardation assays demonstrated that RXR homodimers bind, although with a lower affinity than RAR-RXR heterodimers, to the AH-RXR response element. In conclusion, retinoids induce hepatic apo A-II production at the transcriptional level via the interaction of RXR with an element in the J site containing two imperfect half-sites spaced by 1 oligonucleotide, thereby demonstrating an important role of RXR in controlling human lipoprotein metabolism. Since the J site also confers responsiveness of the apo A-II gene to fibrates and fatty acids via the activation of peroxisome proliferator-activated receptor-RXR heterodimers, this site can be considered a plurimetabolic response element.
Mol Cell Biol 1996 Jul
PMID:Retinoids increase human apolipoprotein A-11 expression through activation of the retinoid X receptor but not the retinoic acid receptor. 866 50

Through expression of the cloned mouse (mSlo) or human (hSlo) large-conductance (BK) Ca(2+)-activated K+ channel in Xenopus laevis oocytes and HEK 293 cells, we characterized the effects of reported blockers and openers of BK channels to initiate the study of the molecular determinants of BK channel modulation. In oocytes, iberiotoxin and charybdotoxin, peptidyl scorpion toxins, were both equally effective blockers of BK current, although iberiotoxin was significantly more potent than charybdotoxin. The structurally related peptide kaliotoxin was not a potent blocker of BK current. Paxilline, a fungal tremorgenic alkaloid, was an effective but complex blocker of BK current. Tetrandrine, a putative blocker of type II BK channels, and ketamine were relatively ineffective. The putative BK openers NS004 and NS1619, phloretin, niflumic acid, flufenamic acid, and 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) increased BK current in oocytes at microM concentrations; many of these produced biphasic concentration-response relationships. Coapplication of representative blockers and openers revealed several patterns of interaction, including competitive and noncompetitive antagonism. NS1619, niflumic acid, and phloretin were tested by using excised inside-out membrane patches from HEK 293 cells and were found to increase the activity of hSlo BK channels and produce a leftward shift in the G/Gmax-versus-voltage relationship of these channels. These results represent the first comprehensive examination of the molecular pharmacology of BK channels.
Mol Pharmacol 1996 Jul
PMID:Effects of channel modulators on cloned large-conductance calcium-activated potassium channels. 870 Jan 14

The present work was carried out to examine the role of glycation and transition metal catalysed autoxidation of sugars in glucose-mediated alterations of myofibrillar proteins. Myofibrils were prepared from rat skeletal muscle and incubated with 1) sugar alone 2) sugar and micromolar concentrations of transition metals (Cu2+ or Fe3+) 3) transition metals alone and the control remained without sugar or transition metals. A significant increase in extent of glycation and decrease in ATPase activity of myofibrils incubated under autoxidative conditions were observed over the other three incubations. Reducing agent 2-mercaptoethanol was highly effective in preventing the alterations induced by glucoxidation, compared to EDTA and aminoguanidine, suggesting the involvement of thiol group oxidation in the reduced function of the protein. Free radical scavengers like catalase, benzoic acid and mannitol were also effective in preventing glucose mediated alterations. Although a high concentration of glucose alone has an insignificant effect on myofibrils in vitro, the results from the present work suggest that glucose in combination with transition metals could lead to functional alterations of myofibrils, and this process by generating free radicals may contribute to the overall complications of diabetes and aging.
Mol Cell Biochem 1996 Jan 26
PMID:The possible relevance of autoxidative glycosylation in glucose mediated alterations of proteins: an in vitro study on myofibrillar proteins. 871 22

Sodium benzoate (SB) therapy is known to increase ammonia (NH3) nitrogen elimination via conjugation with glycine and excretion as urinary hippurate. In 16 children with inborn errors of urea synthesis we studied two issues: (1) the effect of chronic SB administration upon carnitine metabolism and (2) the efficacy of chronic SB therapy as measured by the molar ratio of hippurate excretion to SB intake. Measurements were performed during elective hospitalizations when the patients were in stable metabolic condition. We found that chronic SB therapy is not associated with a constant level of hippurate elimination and that interindividual and intraindividual variability may result in irregular removal of NH3 nitrogen. This variability may be due to various factors including the formation of small quantities of benzoylcarnitine, which was detected in the plasma of three of four patients receiving SB and carnitine therapy and in one of two patients on SB therapy without carnitine supplementation. The ratios of acyl to free carnitine were elevated in both plasma and urine in patients not receiving carnitine supplementation, but were normal in patients receiving supplementation.
Biochem Mol Med 1996 Feb
PMID:Chronic sodium benzoate therapy in children with inborn errors of urea synthesis: effect on carnitine metabolism and ammonia nitrogen removal. 881 24

Tobacco genes that are induced in response to salicylic acid (SA) treatment with immediate-early kinetics were identified by differential mRNA display. Detailed analysis of IS10a, one cDNA clone identified by this method, revealed induction within 30 min of treatment, with a peak of expression at 3 h, that decayed rapidly thereafter. Treatment with the protein synthesis inhibitor, cycloheximide (CHX), also caused induction of IS10a mRNA to comparable levels, but the IS10a mRNA continued to accumulate after 3 h of induction. In combination, CHX and SA led to a superinduction of IS10a mRNA levels that was also sustained. Half-maximal induction was evident at ca. 100-150 microM SA. In addition to SA, induction of IS10a occurred to varying degrees upon treatment with acetylsalicylic acid, benzoic acid, 2,4-dichlorophenoxyacetic acid, methyl jasmonate, and hydrogen peroxide, whereas treatment with other compounds had no effect. The proteins encoded by IS10a and a second highly homologous cDNA show sequence similarity to UDP-glucose: flavonoid glucosyltransferases.
Plant Mol Biol 1996 Aug
PMID:Identification of an immediate-early salicylic acid-inducible tobacco gene and characterization of induction by other compounds. 884 48


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