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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Forskolin, a potent activator of adenylate cyclase, has been proposed to activate this enzyme by a direct interaction with the catalytic subunit. To test this hypothesis, we examined the effects of forskolin on sperm cyclic AMP content and sperm adenylate cyclase activity. Forskolin or cholera toxin did not increase cyclic AMP content in either bull or boar sperm, whereas the inhibitors of phosphodiesterase, caffeine and methylisobutylxanthine, significantly increased sperm cyclic AMP content. Forskolin, NaF, and guanylimidodiphosphate did not activate the adenylate cyclase of either sperm membranes or cytosol. When homogenates of rat, guinea pig, or bull testes were centrifuged at 100,000 X g, the supernatant was found to contain a forskolin-stimulated adenylate cyclase. Further centrifugation of this 100,000 X g supernatant fraction at 250,000 X g for 3 hr quantitatively sedimented the forskolin-sensitive enzyme activity. We conclude that forskolin does not activate either the cytosolic or membrane-bound adenylate cyclase of mammalian sperm.
Mol Pharmacol 1983 Jul
PMID:Forskolin does not activate sperm adenylate cyclase. 668 55

The regulation of the resting intracellular ionized calcium concentration [( Ca2+]i) has been studied in ferret papillary muscle using the photoprotein aequorin to measure [Ca2+]i. Elevating [Ca2+]o produced an initial rapid increase of [Ca2+]i and tension which then decayed to a steady level. This secondary fall of [Ca2+]i is attributed to a secondary decrease of Ca entry on Na-Ca exchange produced by the known fall of [Na+]i. Replacing external Na by K produced a large transient increase of both [Ca2+]i and tension which then decayed spontaneously to near the resting level. If Na was removed after metabolic inhibition with cyanide and deoxyglucose then neither tension nor [Ca2+]i recovered. The addition of the mitochondrial uncoupler FCCP to a muscle in Na-free solution produced a gradual rise of tension but only elevated [Ca2+]i after a delay of many minutes. Similarly caffeine did not elevate [Ca2+]i. These experiments do not support the hypothesis that the regulation of resting [Ca2+]i in Na-free solutions depends solely on intracellular sequestration of [Ca2+]i. The first twitch elicited in Na-containing solutions after exposure to Na-free solution was much larger than control and was associated with a large Ca transient attributed to increased loading of the sarcoplasmic reticulum with Ca in the Na-free solution. The elevation of [Ca2+]i in Na-free solutions was accompanied by spontaneous fluctuations of both [Ca2+]i and tension with a frequency of about 3 Hz. These fluctuations were abolished by drugs such as caffeine or ryanodine which interfere with sarcoplasmic reticulum function. These results provide direct evidence for the spontaneous release of Ca from the sarcoplasmic reticulum inferred from previous, less direct, work.
J Mol Cell Cardiol 1984 Feb
PMID:Control of intracellular ionized calcium concentration by sarcolemmal and intracellular mechanisms. 671 90

Delayed afterdepolarizations have recently been recognized as their important contributions to the genesis of arrhythmias, [3, 6]. This paper deals with the possible causes of the delayed afterdepolarizations and aftercontractions in low K+, high Ca2+ solutions. Simultaneous recordings of membrane potential and tension were employed in dog papillary muscles. The dependence of the amplitude of the delayed afterdepolarizations and the aftercontractions on stimulus frequency and duration of stimulus trains was examined. In addition, effects of isoproterenol, verapamil, caffeine and procaine on both activities were examined. Our results show that conditions causing Ca2+ -overload in the cell provided the development or the augmentation of them. Further, caffeine eliminated oscillatory fluctuations in both activities followed by a transient increase after the treatment and procaine reversibly abolished them. These results support the hypothesis that the delayed afterdepolarizations are caused by a cyclic release of Ca2+ from the sarcoplasmic reticulum under the conditions of Ca2+-overload.
J Mol Cell Cardiol 1984 Mar
PMID:Regulation of delayed afterdepolarizations and aftercontractions in dog ventricular muscle fibres. 671 94

The effect of atenolol, propranolol, trifluoperazine, and caffeine on the occurrence of meiotic diploid and disomic products in Saccharomyces cerevisiae was investigated. We demonstrated that atenolol, propranolol, and trifluoperazine reduce the occurrence of meiotic diploid products and that propranolol also slightly decreases the spontaneous frequency of disomics. On the other hand, caffeine appears to be a powerful inducer of diploid meiotic products, but also shows a lesser effect on disomic induction. Since spontaneous or caffeine-induced diploids arise from a failure of the second meiotic division, it appears that the target of these drugs is at the beginning of the second meiotic division. The only common effect of trifluoperazine and propranolol, mainly investigated in mammals, was an inhibition of calmodulin activity via direct interaction. We tend, therefore, to believe that calmodulin activity must be a crucial point for the second meiotic division to begin. The increased induction of diploids, due to caffeine, may be interpreted as a consequence of an increased cyclic AMP level.
Mol Cell Biol 1982 Nov
PMID:Propranolol, atenolol, and trifluoperazine reduce the spontaneous occurrence of meiotic diploid products in Saccharomyces cerevisiae. 676 80

Studies of nuclear and chloroplastic-DNA repair after ultraviolet irradiation of Euglena gracilis show that photoreactivation is very efficient at both the nuclear and chloroplastic level. Liquid-holding or split-dose experiments and treatment with caffeine reveal, furthermore, that dark-repair is very efficient in nuclear DNA but not in chloroplastic DNA (ctDNA). The possibility of a chloroplastic dark-repair of restricted efficiency is discussed. Determination of chloroplastic DNA content by reassociation kinetics indicates that an important degradation follows UV irradiation during liquid holding in the dark.
Mol Gen Genet 1980
PMID:Comparative studies of chloroplastic and nuclear DNA repair abilities after ultraviolet irradiation of Euglena gracilis. 693 May 37

The mutation frequency of DNA polymerase mutants of phage T4 treated with ethyl methanesulfonate (EMS) then incubated in the presence and absence of caffeine was studied using an rII reversion system. The DNA polymerase mutation is shown to be antimutagenic for EMS induction of reversions which occur by a GC to AT transition. Caffeine acts as a comutagen for the induction by EMS of mutant phages and produces a significant increase in the frequency of reversions from rII to r+. Caffeine is slightly mutagenic for the phage strain carrying the wild type polymerase and inhibits the action of the 3' leads to 5' exonuclease function of T4 DNA polymerase as measured in vitro. These findings suggest that caffeine acts by directly influencing nucleotide selection or the editing function of the DNA polymerase.
Mol Gen Genet 1980
PMID:Caffeine as a comutagen for ethylmethanesulfonate in strains of phage T4. 693 94

Doxorubicin (adriamycin) forms molecular associations with other aromatic and planar molecules (hetero-association) and with other doxorubicin molecules (self-association) in aqueous solution. The ability of doxorubicin to form complexes was demonstrated in a nonbiological system by measuring the doxorubicin partition coefficient. A decreased apparent doxorubicin activity coefficient in the presence of complex formation was also demonstrated in a biological system by measuring the transmembranous doxorubicin transport and the doxorubicin distribution at equilibrium in human red blood cells and their suspending medium. Doxorubicin formed complexes in aqueous solution at 37 degrees (pH 7.3) with (a) DNA-derived bases, nucleosides, and nucleotides; (b) amino acids such as tryptophan; (c) proteins such as human serum albumin and hemoglobin; and (d) a broad range of biologically active compounds such as NAD, propanthelline, caffeine, chloroquine, imipramine, and propranolol. The apparent thermodynamic quantities of the complex formation with adenosine 5'-triphosphate were delta H0, -9.5 kcal . mole-1; delta S0, -19 eu . mole-1; and delta G0 (310 degrees K), -3.6 kcal . mole-1. The binding forces of the molecular associations were probably hydrophobic (short-range force), sometimes supported by electrostatic interaction (long-range force).
Mol Pharmacol 1982 Jul
PMID:Molecular association between doxorubicin (adriamycin) and DNA-derived bases, nucleosides, nucleotides, other aromatic compounds, and proteins in aqueous solution. 712 47

1. Indirect and direct twitch (0.1-Hz) stimulation of the rat phrenic nerve-diaphragm disclosed that the inhibitory effect of HgCl2, 3.7 x 10(-5) M, on the neuromuscular transmission and in the muscle cell, was accelerated by 10-sec periods of 50-Hz tetanic stimulation every 10 min. This activity-dependent enhancement suggested an inhibitory mechanism of HgCl2 related to the development of fatigue, like membrane depolarization or decreased excitability, decreased availability of transmitter, or interference with the factors controlling excitation-secretion coupling of the nerve terminal, i.e. (Ca2+)0 or (Ca2+)i, and excitation-contraction coupling in the muscle cell, i.e., (Ca2+)i. 2. During both indirect and direct stimulation, HgCl2-induced inhibition was enhanced markedly by pretreatment with caffeine, which releases Ca2+ from endoplasmic and sarcoplasmic reticulum in the nerve terminal and muscle cell, respectively. This caffeine-induced enhancement was completely antagonized by dantrolene, which inhibits the caffeine-induced release. However, dantrolene alone did not antagonize the HgCl2-induced inhibition. 3. Since caffeine depletes the intracellular Ca2+ stores of the smooth endoplasmic reticulum, HgCl2 probably inhibits by binding to SH groups of transport proteins conveying the messenger function of (Ca2+)i. In the muscle cell this leads to inhibition of contraction. In the nerve terminal, an additional enhancement of the HgCl2-induced inhibition, by inhibiting reuptake of choline by TEA and tetanic stimulation, suggested that HgCl2 inhibited a (Ca2+)i signal necessary for this limiting factor in resynthesis of acetylcholine. 4. The (Ca2+)0 signal necessary for stimulus-induced release of acetylcholine was not affected by HgCl2. Hyperpolarization in K(+)-free solution antagonized the inhibitory effect of HgCl2 at indirect stimulation, and Ca(2+)-free solution enhanced the inhibitory effect at direct stimulation. K+ depolarization, membrane electric field increase with high Ca2+, membrane stabilization with lidocaine, and half-threshold stimulation, did not change the inhibitory effect of HgCl CH3HgCl. 1.85 x 10(-5) M, disclosed a synergistic interaction with caffeine during direct, but not during indirect, stimulation.
Cell Mol Neurobiol 1994 Dec
PMID:Inhibitory effects of HgCl2 on excitation-secretion coupling at the motor nerve terminal and excitation-contraction coupling in the muscle cell. 754 23

This review summarizes the main cellular mechanisms involved in potassium regulation in plasma and skeletal muscle during exercise. The effects of exercise-induced hyperkalemia and post-exercise hypokalemia on the cardiac action potential are reviewed in light of recent research on Na+ and K+ channel activity. Specific consideration is given to K+ release from contracting skeletal muscle, K+ uptake by contracting skeletal muscle, K+ uptake by non-contracting tissues during the period of exercise, and K+ uptake by skeletal muscle recovering from contractile activity. The onset of exercise is associated with a net release of K+ from contracting skeletal muscle that results in an increase in plasma [K+]. Resultant decreases in intracellular [K+] and increases in interstitial [K+] in contracting skeletal muscle have been implicated in the fatigue process. The rate and magnitude of increase in plasma [K+] is dependent on exercise intensity, trained state of the individual, and on drugs such as beta-adrenoceptor blockers and caffeine. During exercise, the uptake of K+ from the blood by non-contracting tissues may be important in preventing plasma [K+] from rising to excessive levels that will impair skeletal muscle and myocardial excitability and contractility. Cessation of exercise results in a rapid decrease in plasma [K+], often to 3 mEq/l or less with intense exercise, that may be maintained for prolonged periods. The rapid increases and decreases in plasma [K+] with onset and cessation of exercise, respectively, has been implicated in altered myocardial function and sudden cardiac death. Recent studies suggest that increases in catecholamines during exercise are cardioprotective to the arrhythmogenic effects of hyperkalemia.
J Mol Cell Cardiol 1995 Apr
PMID:Potassium regulation during exercise and recovery in humans: implications for skeletal and cardiac muscle. 756 98

Antigenic stimulation of rat basophilic leukemia cells releases Ca2+ from internal stores and increases membrane permeability to Ca2+. The delta isomer of hexachlorocyclohexane (delta-HCH) is structurally similar to myo-inositol-1,4,5-trisphosphate (IP3) and is a potent releaser of stored Ca2+ from permeabilized cells. This release of Ca2+ is not mediated by a competitive interaction with the IP3 receptor on the Ca2+ release channel on the endoplasmic reticulum. In intact cells, delta-HCH and, to a lesser extent, lindane (gamma-hexachlorocyclohexane) transiently increase the intracellular Ca2+ concentration. The return to basal concentrations is mediated by the plasma membrane Ca2+ pumps and not by resequestration of Ca2+ into intracellular stores. Treatment of cells with delta-HCH (25-100 microM), but not lindane, leads to a progressive inhibition of the antigen- and thapsigargin-stimulated Ca2+ signal. Caffeine, a modulator of the ryanodine receptor Ca2+ channel, attenuates the rise in intracellular Ca2+ induced by delta-HCH, suggesting that ryanodine receptor-like Ca2+ channels may be present in RBL cells. At 25 microM delta-HCH, a concentration that does not inhibit the antigen-stimulated Ca2+ signal, the release of [3H]serotonin from antigen-stimulated cells is enhanced as is secretion of [3H]serotonin from cells pretreated with 25-100 microM lindane. The depletion of Ca2+ from intracellular stores by delta-HCH should evoke Ca2+ entry into the cells by a capacitative mechanism; however; divalent cation permeability across the plasma membrane (Mn2+ influx) is not increased but rather is decreased by delta-HCH. An understanding of the mechanism of action of delta-HCH in releasing stored Ca2+ and blocking Ca2+ influx across the plasma membrane may provide insights into the regulation of capacitative Ca2+ entry in nonexcitable cells.
Mol Pharmacol 1995 Sep
PMID:The delta isomer of hexachlorocyclohexane induces rapid release of the myo-inositol-1,4,5-trisphosphate-sensitive Ca2+ store and blocks capacitative Ca2+ entry in rat basophilic leukemia cells. 756 33


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