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)

N-Formyl-L-methionyl-L-leucyl-L-phenylalanine (fMet-Leu-Phe) stimulation of human neutrophils leads to a rapid increase of the cytosolic free Ca2+ concentration, [Ca2+]i, which is significantly reduced by removal of extracellular calcium. In the present study we show that fMet-Leu-Phe-induced [Ca2+]i increases are, in part, mediated by an increase of the plasma membrane permeability to Ca2+. This conclusion is based on the following evidence. In the presence of extracellular calcium, addition of La3+ reduced the fMet-Leu-Phe-induced [Ca2+]i increase to approximately the same level as that observed in the absence of extracellular calcium. A net increase of the plasma membrane permeability for Mn2+ could be observed after fMet-Leu-Phe stimulation, as revealed by intracellular quenching of the quin2 signal. The influx of Mn2+, like that of Ca2+, was inhibited by La3+ and was more pronounced in the absence of extracellular Ca2+, suggesting competition for the same pathway. Temporal dissociation of intracellular Ca2+ release from stores and Ca2+ influx from the medium could be demonstrated by readdition of calcium to cells stimulated in the absence of this cation. This second [Ca2+]i increase could be abolished either by giving the specific chemotactic peptide receptor antagonist, BOC-Met-Leu-Phe, or Co2+. We could also show that the fMet-Leu-Phe-dependent Ca2+ influx was not due to the activation of voltage-dependent calcium channels since depolarization either by K+ or gramicidin D did not affect the resting [Ca2+]i, nor did it affect a subsequent [Ca2+]i increase induced by fMet-Leu-Phe. Furthermore, nifedipine and verapamil, at concentrations known to block classical voltage-dependent calcium channels, had no significant effects on the Ca2+ influx induced by fMet-Leu-Phe. We suggest that fMet-Leu-Phe promotes influx of Ca2+ ions across the plasma membrane of human neutrophils by opening of receptor-dependent calcium channels.
Mol Pharmacol 1986 Nov
PMID:Characterization of fMet-Leu-Phe receptor-mediated Ca2+ influx across the plasma membrane of human neutrophils. 243 Jan 68

1. Maitotoxin (MTX) was an extraordinarily potent stimulant of phosphoinositide breakdown in the neuroblastoma hybrid NCB-20 cells. 2. Maximal responses were obtained at 0.25-0.5 ng MTX/ml, and resulted in increased formation of [3H]inositol mono-, bis-, and trisphosphates. Increased formation of [3H]inositol bis- and trisphosphate was observed as early as 15 sec after the addition of MTX. 3. MTX-induced phosphoinositide breakdown in NCB-20 cells was not antagonized by organic (nifedipine, methoxyverapamil) or inorganic (Mn2+, Co2+, Cd2+) calcium channel blockers. However, the response on phosphoinositide breakdown was completely eliminated in the absence of extracellular calcium. 4. The results suggest that MTX either directly stimulates phosphoinositide breakdown in a calcium-dependent manner or acts indirectly through calcium channels insensitive to organic/inorganic calcium channel blockers.
Cell Mol Neurobiol 1987 Sep
PMID:Maitotoxin stimulates phosphoinositide breakdown in neuroblastoma hybrid NCB-20 cells. 244 66

The voltage- and time-dependent slow channels in the myocardial cell membrane are the major pathway by which Ca2+ ions enter the cell during excitation for initiation and regulation of the force of contraction of cardiac muscle. These slow channels appear to behave kinetically, on a population basis, as if their gates open, close, and recover more slowly than those of the fast Na+ channels. In addition, the slow channel gates operate over a less negative (more depolarized) voltage range. Tetrodotoxin does not block the slow channels, whereas the calcium antagonistic drugs, Mn2+, Co2+, and La3+ ions do. The slow channels have some special properties, including functional dependence on metabolic energy, selective blockade by acidosis, and regulation by the intracellular cyclic nucleotide levels. Because of these special properties of the slow channels, Ca2+ influx into the myocardial cell can be controlled by extrinsic factors (such as autonomic nerve stimulation or circulating hormones) and by intrinsic factors (such as cellular pH or ATP level). During transient regional ischemia, the selective blockade of the slow channels, which results in depression of the contraction and work of the afflicted cells, might protect the cells against irreversible damage by helping to conserve their ATP content. Reperfusion arrhythmias may be caused by the breakdown of this protective mechanism, in that, upon reperfusion, the Ca2+ slow channels may recover before the cells are capable of handling the greater Ca2+ influx (Fig. 20). As depicted in this figure, the Ca2+ slow channels may recover their function before the ATP level is sufficiently recovered to allow bail-out of the intracellular Ca2+. In addition, the generation of free radicals upon reperfusion may injure the Ca-ATPase and other enzymes involved in Ca2+ metabolism. The net effect of this would be to cause Ca2+ overload of the cells and SR, with subsequent delayed after-depolarizations (DADs) leading to triggered automaticity and arrhythmias. Following blockade of the fast Na+ channels in myocardial cells with TTX or by voltage-inactivating them in 25 mM (K)0, catecholamines, angiotensin-II, histamine, and methylxanthines rapidly allow the production of slowly-rising Ca2+-dependent action potentials by increasing the number of Ca2+ slow channels available for voltage activation and/or their mean open time. Concomitantly, these compounds rapidly elevate intracellular cyclic AMP levels, suggesting that cyclic AMP is somehow related to the functioning of the slow channels. Exogenous cyclic AMP produces the same effect, but much more slowly.(ABSTRACT TRUNCATED AT 400 WORDS)
J Mol Cell Cardiol 1988 Mar
PMID:Regulation of calcium slow channels of cardiac muscle by cyclic nucleotides and phosphorylation. 245 7

The effects of the Ca2+ agonist Bay K 8644 on outward potassium currents have been studied in single ventricular cells of chick embryo and aortic single cells of rabbit using the whole-cell patch clamp technique. Bay K 8644 was found to increase 1K in both heart and aortic single cells. This effect of Bay K 8644 on both muscle was reversed by Mn2+ and blocked by 20 mM TEA. The Bay K 8644 potassium I/V curve of single heart cell had a N shape, which is Ca2+ dependent. These data strongly suggest that Bay K 8644 increases a gK(Ca) in both aortic and heart muscle.
Mol Cell Biochem
PMID:Bay K 8644 induce enhancement of K+ current in both single heart cell and smooth muscle cell. 245 1

Several analogues of 2',3'-dideoxythymidine 5'-triphosphate [i.e., 3'-azido-2', 3'-dideoxythymidine 5'-triphosphate(Azdd TTP), 2',3'-didehydro-2',3'-dideoxythymidine 5'-triphosphate (ddeTTP), alpha, beta-methylene 3'-azido-2',3'-dideoxythymidine 5'-diphosphate, alpha, beta-methylene 3'-azido-2',3'-dideoxythymidine 5'-triphosphate, and beta, gamma-methylene 3'-azido-2',3'-dideoxythymidine 5'-triphosphate] and 2',3'-didehydro-2',3'-dideoxycytidine 5'-triphosphate (ddeCTP) have been evaluated for their inhibitory effects on murine retroviral reverse transcriptase and various other DNA polymerases, including DNA polymerases alpha, beta, and gamma, terminal deoxynucleotidyl transferase, and DNA polymerase I. None of the compounds inhibited the activity of DNA polymerase alpha under the reaction conditions employed. When Mg2+ was replaced by Mn2+, however, DNA polymerase alpha was strongly inhibited only by ddeTTP. DNA polymerase beta activity was inhibited only by ddeTTP and ddeCTP. All the compounds, except for ddeCTP, inhibited DNA polymerase gamma activity, ddeTTP being a particularly strong inhibitor of gamma-polymerase (Ki = 3.5 nM). Terminal deoxynucleotidyl transferase was only slightly inhibited by any of the compounds. AzddTTP was a potent inhibitor of reverse transcriptase (Ki = 42 nM), but it also inhibited the activities of DNA polymerase gamma and DNA polymerase I.
Mol Pharmacol 1989 May
PMID:Differential inhibitory effects of several pyrimidine 2',3'-dideoxynucleoside 5'-triphosphates on the activities of reverse transcriptase and various cellular DNA polymerases. 247 Oct 54

The properties of an endogenous RNA-dependent DNA polymerase (reverse transcriptase) associated with retrovirus-like particles (VLP) in a Drosophila melanogaster cell line were characterized. The enzyme requires a monovalent and a divalent cation, a sulfhydril-reducing agent and the four deoxynucleosides triphosphates for a maximal activity. The reaction was enhanced by a detergent and was sensitive to a DNA-A-free RNA-A indicating that the enzymatic activity was indeed associated with VLP which contain intrinsic RNA. The maximal incorporation of the labelled deoxynucleotide was observed at 25 degrees C in the presence of Mn2+. The enzyme responded well to exogenous template-primers in the similar way to that of retroviral reverse transcriptase and the use of several inhibitors confirms the presence of a real reverse transcriptase activity associated with virus-like particles in drosophila cells.
Cell Mol Biol 1989
PMID:Characterization of a reverse transcriptase activity associated with retrovirus-like particles in a Drosophila cell line. 247 94

Strains carrying plasmids that code for 10Sa RNA synthesize a larger molecule when the RNA processing enzyme RNase E is inactivated. The T1 fingerprint of 10Sa RNA and the larger molecule is very similar, but the latter contains additional oligonucleotides. We show that the larger RNA is converted to the smaller, mature RNA. The precursor molecule starts with an adenosine triphosphate and is therefore a primary transcript. RNase E is not the enzyme that processes p10Sa (precursor 10Sa) RNA into 10Sa RNA. The cell extract contains an activity that carries out this conversion. This activity requires the dication Mn2+.
Mol Gen Genet 1989 Jun
PMID:A precursor for a small stable RNA (10Sa RNA) of Escherichia coli. 247 57

We have characterized a chloroplast processing activity that catalyzes the conversion of the plastid cytochrome b6/f subunit IV (pet D) mRNA 3' end precursor to the mature RNA possessing a 3' inverted repeat (IR). In a chloroplast soluble protein extract, the activity requires Mg2+ or Mn2+, but not K+. In the absence of Mg2+, the pet D 3' IR-RNA product does not accumulate, and UV-cross-linking indicates that the 3' IR-RNA precursor binds several new proteins in addition to those previously characterized as part of the 3' IR-RNA: protein complex in vitro. In contrast, high concentrations of Zn2+ or Cu2+ suppress protein binding and inhibit the processing reaction. The purified exoribonuclease polynucleotide phosphorylase (E.C.2.7.7.8) is not efficient in processing the pet D 3' IR-RNA precursor, whereas Escherichia coli ribonuclease II rapidly processes the pet D IR-RNA precursor to a product of a size similar to that of the mature 3' IR-RNA, but also rapidly degrades the mature RNA in the absence of chloroplast extract. We therefore conclude that the maturation of the pet D mRNA in vitro requires specific chloroplast enzymes which process the mRNA 3' end precursor in the absence of efficient transcription termination. The chloroplast enzyme activities are biochemically distinct from their bacterial counterparts. We also note that specific chloroplast components may be required to stabilize the mature pet D mRNA 3' end against further exonucleolytic degradation.
Plant Mol Biol 1989 Dec
PMID:Chloroplast mRNA 3' end maturation is biochemically distinct from prokaryotic mRNA processing. 248 89

The cation and structural requirements of the intracellular inhibitory "P" site of adenylate cyclase were investigated in human platelet membranes, bovine sperm particles, and detergent-solubilized and purified preparations from rat and bovine brain. Sensitivity of adenylate cyclase to P site-mediated inhibition was enhanced by reversible and irreversible activators of the enzyme. The most effective sensitization of the platelet and brain adenylate cyclases was observed with Mn2+ and upon proteolysis with inhibin in the presence of guanosine 5'-O-(3-thiotriphosphate). These resulted in IC50 values for (2',5'dideoxy-adenosine (2',5'-dd-Ado) and 2'-deoxy-3'-AMP of approximately 1-2 microM. The data were consistent with the ideas that P site-mediated inhibition of adenylate cyclase is dependent on divalent cation and is a function of enzyme activity. A number of nucleosides and nucleotides were synthesized and used to define structural requirements for P site-mediated inhibition of a detergent-solubilized adenylate cyclase from rat brain. The data suggest a strict requirement for an intact adenine moiety and a beta-glycosidic linkage for the ribosyl moiety. 2'-Deoxy-and especially 2',5'-dideoxy-ribosyl moieties enhanced sensitivity and a strong preference for phosphate at the 3'-position was exhibited. Substitutions at the 5'-ribose position impaired sensitivity. The order of potency and IC50 values of the more potent adenosine analogs were 2',5'-dideoxy-3'-AMP (congruent to 0.1 microM) greater than 2'-deoxy-3'-AMP (congruent to 1 microM) greater than 2',5'-dd-Ado (congruent to 3 microM) greater than 3'-AMP (congruent to 9 microM) greater than 2'-deoxy-adenosine (congruent to 15 microM) greater than adenosine (congruent to 80 microM). Large substitutions at the 3'-ribose position were tolerated, e.g., dApdN di- and dAp(dN)4 penta-nucleotides and succinyl- and p-fluoro-sulfonyl-benzoyl- moieties. The purified adenylate cyclase from bovine brain was inhibited by P site agonists with IC50 values of 34 and 45 microM for 2'-deoxy-3'-AMP and 2',5'-dd-Ado, respectively. The data imply, first, that the locus of the P site is the catalytic subunit of adenylate cyclase and, second, that the increased sensitivity observed with Mn2+ is due to an effect of the cation on the catalytic subunit. In contrast with adenylate cyclases from other mammalian tissues, the enzyme from bovine sperm exhibited only weak sensitivity to P site agonists; 2'-deoxy-3'-AMP congruent to 2',5'-dd-Ado greater than adenosine, each with IC50 values greater than 1000 microM.(ABSTRACT TRUNCATED AT 400 WORDS)
Mol Pharmacol 1989 May
PMID:Cation and structural requirements for P site-mediated inhibition of adenylate cyclase. 249 37

The effects of Ca-antagonists on the thrombin-induced mobilization of radiolabeled arachidonate preincorporated into rat platelets as well as the subsequent formation of labeled cyclooxygenase and lipoxygenase products were analyzed in the presence of either Ca2+ or Ca2+-substitutes, Sr2+ and Ba2+. Results indicate that following thrombin stimulation (0.2 U/ml) in the presence of Ca2+, nitrendipine (Nit), Cd2+ or Mn2+ reduced the release of arachidonate and the biosynthesis of thromboxane B2. Inhibition of arachidonic acid release and metabolism were also obtained by both Nit and Cd2+ in the presence of Sr2+ and Ba2+. Results from studies with a semi-purified phospholipase A2 fraction prepared from rat platelets indicated that the activity was almost unaffected by Nit or Cd2+. From these findings, we concluded that inhibition of platelet-induced release and metabolism of arachidonic acid by the Ca-antagonists tested require intact platelets. These data support the hypothesis of an interaction of these agents at an unknown surface membrane level.
Mol Cell Biochem 1989 Feb 21
PMID:Effects of organic and inorganic Ca antagonists on rat platelet arachidonic acid metabolism in the presence of Ca2+, Sr2+ and Ba2+. 249 42


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