Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.16.2 (PCP)
 3,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A subpopulation of canine cardiac sarcoplasmic reticulum vesicles has been found to contain a "Ca2+ release channel" which mediates the release of intravesicular Ca2+ stores with rates sufficiently rapid to contribute to excitation-contraction coupling in cardiac muscle. 45Ca2+ release behavior of passively and actively loaded vesicles was determined by Millipore filtration and with the use of a rapid quench apparatus using the two Ca2+ channel inhibitors, Mg2+ and ruthenium red. At pH 7.0 and 5-20 microM external Ca2+, cardiac vesicles released half of their 45Ca2+ stores within 20 ms. Ca2+-induced Ca2+ release was inhibited by raising and lowering external Ca2+ concentration, by the addition of Mg2+, and by decreasing the pH. Calmodulin reduced the Ca2+-induced Ca2+ release rate 3-6-fold in a reaction that did not appear to involve a calmodulin-dependent protein kinase. Under various experimental conditions, ATP or the nonhydrolyzable ATP analog, adenosine 5'-(beta, gamma-methylene)triphosphate (AMP-PCP), and caffeine stimulated 45Ca2+ release 2-500-fold. Maximal release rates (t1/2 = 10 ms) were observed in media containing 10 microM Ca2+ and 5 mM AMP-PCP or 10 mM caffeine. An increased external Ca2+ concentration (greater than or equal to 1 mM) was required to optimize the 45Ca2+ efflux rate in the presence of 8 mM Mg2+ and 5 mM AMP-PCP. These results suggest that cardiac sarcoplasmic reticulum contains a ligand-gated Ca2+ channel which is activated by Ca2+, adenine nucleotide, and caffeine, and inhibited by Mg2+, H+, and calmodulin.
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PMID:Rapid calcium release from cardiac sarcoplasmic reticulum vesicles is dependent on Ca2+ and is modulated by Mg2+, adenine nucleotide, and calmodulin. 243 95

A soluble ATP/Mg2-dependent proteolytic system from rabbit cardiac muscle has been identified (m ca. 310 kDa) and purified ca. 9-fold. This enzyme which splits the substrate [3H]globin and 125I-bovine serum albumin (125I-BSA) has many similarities to the ATP-dependent proteolytic enzyme system from reticulocytes which utilizes ubiquitin: 1) The specific activities in reticulocyte lysates and cardiac muscle extracts are of the same magnitude (0.5-1 arb. unit/mg). 2) The binding and elution behavior on DEAE-cellulose is similar. 3) In both cases the pH optimum (substrate 125I-BSA) is pH 7.6. 4) Both enzymes are inhibited by hemin, NEM and iodoacetate but not e.g. by leupeptin, or inhibitors of serine proteases. 5) Neither enzyme system can utilize ATP-analogs such as AMP-CPP, AMP-PCP, AMP-PNP or ATP-gamma-S. There are however also significant differences: 1) The enzyme system from cardiac muscle is fully active in the absence of ubiquitin and cannot be activated by this peptide. 2) The enzyme from cardiac muscle can degrade methylated BSA. 3) The cardiac muscle enzyme can be further purified on Sepharose 4B; the enzyme from reticulocytes is inactivated by this procedure. 4) The cardiac enzyme cannot be inactivated by ribonuclease as the reticulocyte counterpart. Although ubiquitin does not appear to play a role in the isolated ATP/Mg2-dependent proteolytic system from cardiac muscle, it is demonstrated for the first time that 125I-ubiquitin can be conjugated to a wide variety of cardiac muscle proteins in vitro in an ATP-dependent manner. Apparent molecular masses of major conjugates were: 185 kDa, 140 kDa, 85 kDa, 65 kDa, 46 kDa, 38 kDa and 36 kDa as estimated by discontinuous SDS gel electrophoresis. Addition of purified phosphorylase kinase to cardiac muscle extract changed the ubiquitination pattern by the appearance of two novel protein bands. It is concluded that the ATP/Mg2-dependent proteolytic system of cardiac muscle must be differentiated from the proteolytic system of reticulocytes mainly because of its ubiquitin-independence. Nevertheless the conjugation of 125I-ubiquitin to many muscle proteins is a strong indication for a crucial role of this interesting peptide in striated muscle.
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PMID:ATP-dependent proteolysis and the role of ubiquitin in rabbit cardiac muscle. 304 36

A major approach to the elucidation of the mechanisms by which phencyclidine (PCP) elicits the varied and complex responses observed in biological systems consists of comparisons of the pharmacological profiles of PCP derivatives with those of drugs for which the mechanism of action is better understood. Such studies depend on the definition of discriminant structure-activity relationships and on comparisons of rank orders of potency for the actions of PCP derivatives. Using the muscarinic cholinergic system in brain and the potassium ion channels in cardiac muscle as targets for PCP derivatives, we review the elucidation of the structural determinants for PCP recognition at muscarinic receptors, and the dramatic effect of assay conditions on the rank order of potency for the action of PCP derivatives at intracellular sites. The structural and physicochemical considerations illustrated here must be considered basic to the establishment of any assay aimed at the elucidation of the mechanism of action of PCP.
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PMID:Multiple actions of phencyclidine: discriminant structure-activity relationships from molecular conformations and assay conditions. 630 61

[3H]Ryanodine binding to, as well as functions of, ryanodine receptor intracellular Ca2+ release channel complexes are modulated by several adenosine-based compounds. In this study, we determined the effects of endogenous compounds termed diadenosine polyphosphates (ApnAs; n = 2-6 phosphate groups) on [3Hlryanodine binding to membranes prepared from rat brain and skeletal and cardiac muscle. Under low ionic strength buffer conditions, [3H]ryanodine binding to brain membranes was significantly increased by 171% with 333 microM P1,P5-di(adenosine-5') pentaphosphate (Ap5A) and by 209% with the same concentration of the metabolism-resistant ATP analogue betagamma-methyleneadenosine 5'-triphosphate (AMP-PCP) compared with control values for [3H]ryanodine binding of 9.6 +/- 1.8 fmol/mg of protein. Dose-related increases in [3H]ryanodine binding were observed for all five ApnAs tested [P1,P2-di(adenosine-5') pyrophosphate (Ap2A), P1,P3-di(adenosine-5') triphosphate (Ap3A), P1,P4-di(adenosine-5') tetraphosphate (Ap4A), Ap5A, and P1,P6-di(adenosine-5') hexaphosphate (Ap6A)] as well as AMP-PCP; oxidized salts of ApnAs stimulated [3H]ryanodine binding to a greater degree than did nonoxidized APnAs. The apparent rank order for the capacity of these agents to increase [3H]-ryanodine binding was oxidized Ap4A = oxidized Ap5A > oxidized Ap3A > Ap6A > AMP-PCP > Ap5A > AP2A. Addition of the approximate EC50 dose of oxidized Ap4A (37 microM) increased the affinity (KD) of ryanodine receptors from 34 +/- 7 to 12 +/- 2 nM, the apparent binding site density (Bmax) was not significantly different from control values of 107 +/- 33 fmol/mg of protein. Increases in [3H]-ryanodine binding by either oxidized Ap4A or nonoxidized Ap5A were not further enhanced by coincubation with AMP-PCP, which suggests a similar site of action for the ApnAs and AMP-PCP. [3H]Ryanodine binding to skeletal and cardiac muscle membranes was enhanced by addition of oxidized AP4A Ap5A, and AMP-PCP. Oxidized AP4A increased the specific binding by ninefold in skeletal muscle and by threefold in cardiac muscle. These results suggest that ApnAs, at physiologically relevant concentrations, may serve as endogenous modulators of ryanodine receptor-gated Ca2+ release channels.
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PMID:Regulation of ryanodine receptor calcium release channels by diadenosine polyphosphates. 876 82

The properties of a ryanodine-sensitive Ca2+ release channel (receptor) in non-excitable cells like exocrine cells or epithelial cells are described in this review. The ryanodine-sensitive Ca2+ release from the microsomal vesicles is activated by Ca2+, caffeine, ryanodine or cyclic ADP-ribose (cADPR) and is inhibited by ruthenium red or higher concentrations (> or =100 microM) of ryanodine. The properties are similar to those of excitable cells such as muscle cells or neuronal tissues. In some non-excitable cells, the Ca2+ release induced by caffeine, ryanodine or cADPR is stimulated by calmodulin (CaM) or FK506. Kd values of [3H]ryanodine binding to the receptor protein range from 6 to 17 nM and are similar to those of a high-affinity binding site in skeletal or cardiac muscle. Maximum binding capacities (Bmax) range from 40 to 620 fmol/ mg protein and are 10 approximately 200-fold lower than those for a high-affinity binding site in skeletal muscle. Caffeine, adenine nucleotide AMP-PCP, Mg2+, ruthenium red or FK506 affects the binding. In some non-excitable cells, the ryanodine receptor (RyR) isoform RyR2 or RyR3 is expressed and has been identified. However, unlike for excitable cells, information concerning the RyR proteins, including binding sites for modulators like CaM and phosphorylation sites has not yet been obtained.
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PMID:Ryanodine-sensitive Ca2+ release mechanism in non-excitable cells (Review). 1111 3