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

Calcium is believed to provide feedback between myocardial energy consumption and production. Calcium content was proved to increase in mitochondria (MT) isolated from (1) stimulated hearts, and (2) hearts of increased contractility. In this work we compared Ca2+ content in the intact MT of skinned strips excised at 0 degrees C from previously stimulated or rested guinea-pig ventricles equilibrated with 45Ca and in single rested or stimulated myocytes. In both preparations Ca2+ was released from MT by means of CCCP (carbonyl cyanide m-chlorophenyl-hydrazone; 100 microM). CCCP released 1.58 +/- 0.55 nmol Ca2+/mg of MT protein from the strips of rested hearts and 3.86 +/- 1.12 nmol Ca2+/mg of MT protein from the stimulated muscles. Stimulated myocytes responded to the close micro-injection of CCCP with transient contracture which was not inhibited by caffeine (10 mM) or ryanodine (0.1 microM, 45 min), although the time-course of the contracture was changed. Contracture could not be initiated in rested cells. It is suggested that in rested myocytes MT contain much less Ca2+ than in stimulated ones.
J Mol Cell Cardiol 1991 Feb
PMID:Calcium in the in situ mitochondria of rested and stimulated myocardium. 206 28

We investigated the effects of the physiological neurotransmitter norepinephrine on the contractile properties and Ca2+ dynamics of isolated cardiac myocytes, with particular emphasis on possible interactions between alpha- and beta-adrenergic effects. Individual rat ventricular myocytes were electrically stimulated at a frequency of 1 Hz. Norepinephrine (10(-9) to 10(-5) M) increased extent and velocity of shortening and decreased the contraction duration. beta-Adrenergic activation gave a greater enhancement of extent and velocity of shortening than did norepinephrine alone (i.e. alpha plus beta). Neither alpha 1 nor alpha 2 adrenergic activation individually produced a significant impact upon contraction. Using suspensions of myocytes loaded with Quin-2, we also studied resting levels of cytosolic Ca2+ ([ Ca2+]c), the increase of [Ca2+]c due to caffeine-addition (as an index of sarcoplasmic reticulum Ca2+ content) and the subsequent increase in [Ca2+]c due to depolarization with 30 mM K+ (as an index of sarcolemmal voltage-dependent Ca2+ channel activity). Norepinephrine decreased resting [Ca2+]c, increased sarcoplasmic reticulum Ca2+ content and increased Ca2+ channel activity. beta-Adrenergic activation produced the same effect on resting [Ca2+]c and sarcoplasmic reticulum content, but gave significantly greater activation of sarcolemmal Ca2+ channel activity, than did norepinephrine (alpha plus beta). By contrast, alpha-adrenergic stimulation had no effect on resting [Ca2+]c or sarcoplasmic reticulum Ca2+ content. We conclude that beta-mediated effects predominate in the action of the physiological agonist norepinephrine on cardiac myocytes. However, alpha (specifically alpha 1)-adrenergic effects are significant in diminishing the potentiation of the extent and velocity of shortening, and of depolarization-induced entry of Ca2+ into the cell, which is seen on beta-stimulation alone. Thus, there may be an intrinsic feedback effect in the actions of norepinephrine on the cardiac myocyte.
J Mol Cell Cardiol 1990 Jan
PMID:Interactive alpha- and beta-adrenergic actions of norepinephrine in rat cardiac myocytes. 215 52

Rat cardiac membrane vesicles enriched in biochemical markers of the junctional region of sarcoplasmic reticulum (SR) and exhibiting ruthenium red-sensitive rapid Ca2+ release have been prepared. Doxorubicin and seven congeners are shown to enhance the binding of [3H]ryanodine to the ryanodine receptor with a strong structural requirement. Doxorubicin enhances the binding of [3H]ryanodine to SR membranes and soluble receptor preparations and induces Ca2+ release from SR vesicles in a highly Ca2(+)-dependent manner, suggesting that anthraquinones promote the open state of the junctional Ca2+ release channel by increasing the affinity of the Ca2+ activator site for Ca2+. Doxorubicin reduces the Kd of [3H]ryanodine binding solely by enhancing the rat of association. Caffeine competes for the same site with anthraquinones, because the caffeine-activated binding of [3H]ryanodine is inhibited by doxorubicin and vice versa. The acute effect of doxorubicin on the cardiac Ca2+ release channel is fully reversible; however, long term treatment (up to 24 hr) with doxorubicin increases the sensitivity of the preparation to subsequent acute challenge with doxorubicin. The thiol-reductive agent dithiothreitol enhances, whereas the reactive disulfide 4,4'-dithiodipyridine reduces, the doxorubicin-enhanced binding of [3H]ryanodine. These results demonstrate that the acute and chronic cardiotoxicity of anthraquinones may be accounted for by a receptor-mediated mechanism. Our findings suggest that the chronic effects observed with the clinical use of anthraquinones may be the result of a receptor-mediated shift in the redox equilibrium of allosteric thiols at the ryanodine receptor complex, which in turn leads to long term sensitization of the Ca2+ release channel.
Mol Pharmacol 1990 Apr
PMID:Anthraquinone-sensitized Ca2+ release channel from rat cardiac sarcoplasmic reticulum: possible receptor-mediated mechanism of doxorubicin cardiomyopathy. 215 59

A crude preparation of heavy sarcoplasmic reticulum (HSR) was isolated using 1 gram of muscle obtained from swine susceptible to malignant hyperthermia (MH) and from control swine. The caffeine and ATP concentration-dependency of Ca-release was determined using suction filtration with radioisotopic 45Ca as a tracer. Rates of release were determined using a rapid filtration system. Caffeine and ATP-induced Ca-release from MH-susceptible (MHS) HSR occurred at one-tenth the concentration of agonist that was required for control muscle HSR. No differences in rates and amounts of release were observed when agonist concentrations were used that caused maximum release for controls. However, at the threshold concentration of caffeine causing release for control HSR, the MHS HSR released 4-times as much Ca and at 3-times the rate of controls. These findings indicate that increased rates and amounts of Ca-release are due to the hypersensitivity of the Ca-release channel of HSR and that this abnormality can be detected using 1 gram of muscle.
Mol Cell Biochem 1990 Mar 05
PMID:Microassay for malignant hyperthermia susceptibility: hypersensitive ligand-gating of the Ca channel in muscle sarcoplasmic reticulum causes increased amounts and rates of Ca-release. 215 20

The EDTA-resistant cell-cell adhesion expressed at the aggregation stage of Dictyostelium discoideum is mediated by a cell surface glycoprotein of Mr 80,000 (gp80). The expression of gp80 is developmentally regulated by cyclic AMP (cAMP). In vitro nuclear run-on experiments show that transcription of the gp80 gene is initiated soon after the onset of development. The basal level of gp80 transcription is significantly augmented by exogenous cAMP pulses. Interestingly, in analog studies, 2'-deoxy-cAMP, 8-bromo-cAMP, and N6-monobutyryl-cAMP are all capable of inducing a rapid accumulation of gp80 mRNA, suggesting the presence of a unique cAMP receptor that responds equally well to these analogs. To determine whether intracellular cAMP plays a role in the regulation of gp80 expression, caffeine was used to block cAMP-induced receptor-mediated adenylate cyclase activation. Expression of gp80 mRNA was blocked in caffeine-treated cells but could be substantially restored by treatment with exogenous cAMP pulses, suggesting that adenylate cyclase activation is not required. gp80 expression was also examined in the signal transduction mutants synag 7 and frigid A. In both mutants, gp80 was expressed at the basal level. Pulses of cAMP as well as 2'-deoxy-cAMP and N6-monobutyryl-cAMP were capable of restoring the normal level of gp80 expression in synag 7 cells. These results, taken together, indicate bimodal regulation of gp80 expression during development and the involvement of a novel cAMP receptor in the transmembrane signalling pathway that regulates gp80 gene expression.
Mol Cell Biol 1990 Jul
PMID:A pharmacologically distinct cyclic AMP receptor is responsible for the regulation of gp80 expression in Dictyostelium discoideum. 216 72

Caffeine potently inhibited forskolin-stimulated cyclic AMP accumulation in slices of rat cerebral cortex, with an IC50 of 21 +/- 3 microM. Because caffeine competitively blocks adenosine receptors, we examined whether the action of forskolin involved endogenous adenosine or whether caffeine was acting through some novel mechanism. Inhibition by caffeine was observed at all forskolin concentrations examined, although the degree of inhibition decreased at higher concentrations of forskolin. The effect of caffeine was not blocked by the presence of a phosphodiesterase inhibitor but was mimicked by several other methylxanthines. The most potent of these was 8-(p-sulfophenyl)-theophylline, which does not readily cross cell membranes, arguing for an extracellular site of action. Addition of either adenosine or the adenosine uptake blocker dipyridamole potentiated the forskolin response, suggesting that forskolin and adenosine act synergistically in increasing cyclic AMP accumulation. The nonxanthine adenosine receptor antagonist CGS 15943 potently blocked cyclic AMP responses to forskolin, adenosine, and combinations. 3-Isobutyl-1-methylxanthine potently blocked the response to adenosine but caused little or no inhibition of the response to forskolin. Adenosine deaminase (ADA) was added to eliminate contributions of endogenous adenosine. ADA inhibited the response to both adenosine and forskolin; however, 200 times as much enzyme was necessary to inhibit the forskolin response. Inhibition of added ADA with 2'deoxycoformycin dramatically increased the concentration of ADA required to inhibit the adenosine response, without altering the concentration required to inhibit the forskolin response. These results suggest that forskolin-stimulated cyclic AMP accumulation may be partially dependent on endogenous adenosine but that the inhibition observed with caffeine is not solely due to blockade of adenosine receptors.
Mol Pharmacol 1990 Nov
PMID:Is adenosine involved in inhibition of forskolin-stimulated cyclic AMP accumulation by caffeine in rat brain? 217 72

In vitro fertilizing ability of stallion spermatozoa was assessed using horse follicular oocytes matured in vitro. After collection, stallion spermatozoa were either: 1) washed and incubated in TALP medium with 3 mg/ml bovine serum albumin (BSA) and 10 micrograms/ml heparin for 4h, 2) washed and incubated in TALP with 3 mg/ml BSA for 3 h and cultured for a further 1 h with 1 mM caffeine and 5 mM dbcAMP, 3) washed and incubated in TALP medium with 3 mg/ml BSA at pH 7.9-8.2 for 2-4 h, or 4) diluted and incubated in TALP medium with 10 mg/ml BSA and 7.14 microM calcium ionophore A 23187 for 5-10 min followed by washing. After a given pretreatment, suspensions were diluted into B2 medium to a concentration of 5 x 10(6) sperm/ml and co-incubated with oocytes for 12 h or 24-48 h. In the ionophore-treated group, 18 of 54 oocytes (33%) were fertilized by 12 h, and 11 of 45 (24%) cleaved by 24-48 h. Evidence of fertilization was not found in the oocytes incubated with spermatozoa from other treatment procedures.
Mol Reprod Dev 1990 Aug
PMID:In vitro fertilization of horse follicular oocytes matured in vitro. 222 85

This study was designed to examine the effects of hypoxia, acidosis, glucose-free medium and their combination on contraction and sarcoplasmic reticulum (SR) function in rat ventricular trabeculae. The isometric twitch tension was measured during superfusion with hypoxic (PO2 less than 30 mmHg), acidic (pH 6.80), glucose-free, or their combined ("ischemic") Tyrode's solution at 20 degrees C. The time needed to fully recover the contraction induced by 10 mM caffeine (repriming time) was measured to indirectly estimate the Ca2+ uptake of the SR. In "ischemia" and acidosis, the peak developed tension decreased progressively for the first 30 min (37.6 +/- 9.2% and 56.6 +/- 8.4% of control at 30 min, respectively), and then became steady. In hypoxic solution, the peak developed tension decreased moderately for the first 30 min (86.8 +/- 4.8% of control at 30 min), and thereafter remained steady. Developed tension did not change significantly during 60 min of superfusion with glucose-free solution. The repriming time of caffeine contraction was significantly delayed in both "ischemic" and hypoxic solutions, but was unchanged in acidic and glucose-free solutions. These results lead us to suggest that depressed SR function to accumulate Ca2+ may contribute to the decline in tension in ischemia and hypoxia, but that other mechanisms are important in the tension decline induced by acidosis.
J Mol Cell Cardiol 1990 Jun
PMID:Effects of hypoxia, acidosis, and simulated ischemia on repriming of caffeine contracture in rat myocardium. 223 37

We tested Shattock and Bers' (1989) hypothesis according to which in rat cardiac myocytes net Ca2+ influx during diastole via Na/Ca exchange provides the main route of entry of Ca2+ available for activation of contractions. We used injections of caffeine into the close vicinity of the single, isolated rat or guinea-pig ventricular myocytes in order to release Ca2+ from sarcoplasmic reticulum (SR). The cells responded to caffeine with a transient contracture, the amplitude of which was regarded as a relative index of SR Ca2+ content. Application of caffeine deprived the SR of Ca2+. This was manifested by a very small (rat) or absent (guinea-pig) contractile response to the second application of caffeine and by a decrease of the amplitude of the first post caffeine contraction to 8 +/- 3% (rat) or to 16 +/- 6% (guinea-pig) of control. In the rat myocytes SR deprived of Ca2+ was able to recover its Ca2+ store even in the resting cell. This was indicated by the time dependent recovery of contractile response to the second application of caffeine and of the amplitude of the post-caffeine electrically evoked contractions. The recovery of post-caffeine contractile responses was completely inhibited by Ca2+ free solution, by 5.0 mM Ni+ and by low K+ (1.0 mM) hyperpolarising solution superfused from the first application of caffeine or during rest. The recovery was enhanced by superfusion of the cells with low Na+ (50%) solution. These results show that there is a considerable net Ca2+ influx by means of Na/Ca exchange and then the SR Ca2+ uptake in the resting rat myocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Cell Cardiol 1990 Nov
PMID:Net Ca2+ influx and sarcoplasmic reticulum Ca2+ uptake in resting single myocytes of the rat heart: comparison with guinea-pig. 228 83

Platelet aggregation and secretion are associated with a rise in intracellular calcium concentration ([Ca2+]i). Adenosine has been postulated as an endogenous inhibitor of platelet aggregation. The antiaggregatory effects of adenosine are related to activation of adenylate cyclase. We studied the effect of adenosine on the rise in [Ca2+]i and platelet aggregation produced by thrombin. Human platelets were obtained from dextrose/citrate-treated plasma. [Ca2+]i was determined by fluorescence-dye techniques (fura-2). Adenosine inhibited the slope of the first phase of aggregation and the rise in [Ca2+]i produced by thrombin, in a dose-dependent manner. The dose that produced 50% inhibition of both aggregation and the rise in [Ca2+]i was approximately 500 nM. The effects of adenosine on [Ca2+]i were shared by its stable analogs, 5'-N-ethylcarboxamidoadenosine being approximately 10-fold more potent than (-)N6-phenylisopropyladenosine, suggesting that these effects were mediated through adenosine A2 receptors. Furthermore, caffeine antagonized the inhibitory effects of adenosine on platelet aggregation and [Ca2+]i. The effects of adenosine on [Ca2+]i appear to be mediated through a rise in intracellular cAMP, because they were prevented by the adenylate cyclase inhibitor 2',5'-dideoxyadenosine (1 mM) and were potentiated by phosphodiesterase inhibition with papaverine (1 microM). Adenosine also inhibits the rise in [Ca2+]i produced by thrombin in a calcium-free medium, suggesting that adenosine inhibits both calcium influx and the release of calcium from intracellular stores.
Mol Pharmacol 1990 Jun
PMID:Adenosine inhibits the rise in intracellular calcium and platelet aggregation produced by thrombin: evidence that both effects are coupled to adenylate cyclase. 235 5


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