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

This study was designed to determine whether the various classes of Ca2+ channel blockers have differential protective effects on isolated adult rat ventricular myocytes exposed to high K+ under anoxic (100% N2) conditions. Calcium-tolerant myocytes were incubated under control (4mM K+) aerobic conditions and then subjected to high K+ (75 mM) and N2. The cells were assessed by morphological criteria (i.e. absence of blebbing, granulation etc.), maintenance of ATP levels, exclusion of trypan blue, and the presence or absence of spontaneous contractile activity. Under control conditions, the cells were quiescent and declined at a rate of approximately 10%/h. In the absence of O2, the rate of cell decline was significantly faster. Verapamil, diltiazem and the dihydropyridines had no significant effects on cell decline under these conditions. Cells exposed to 75 mM K0+ exhibited contractile activity and accelerated rate of decline under anoxic conditions; these effects were independent of lowering Na0+ to 75mM. Cells in high K0+ and N2 were significantly protected (i.e. contractile activity and rate of decline were decreased) by verapamil, less so by diltiazem, and not at all by the dihydropyridines. The uptake of 45Ca2+ into cells in high K0+ was not significantly altered by verapamil or diltiazem. Caffeine induced the immediate cessation of contractile activity of cells incubated in high K0+, but did not affect the accelerated rate of cell declined under anoxic conditions. Verapamil and diltiazem still conferred significant protection in this non-beating cell preparation. Neither verapamil nor diltiazem had any effect on the oscillation frequency of skinned heart cells.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Cell Cardiol 1985 Dec
PMID:Differential effects of calcium antagonists on viability of adult rat ventricular myocytes. 408 3

Changes in the molecular weight of nascent DNA made after ultraviolet (UV) irradiation have been studied in the excision-defective Neurospora mutant uvs-2 using isotopic pulse labeling, alkaline gradient centrifugation and alkaline filter elution. Both the size of nascent DNA and the rate of incorporation of label into DNA was reduced by UV light in a dose dependent manner. However, this DNA repair mutant did recover the ability to synthesize control-like high molecular weight DNA 3 hours after UV treatment, although the rate of DNA synthesis remained depressed after the temporary block to elongation (or ligation) had been overcome. Photoreactivation partially eliminated the depression of DNA synthesis rate and UV light killing of cells, providing strong evidence that the effects on DNA synthesis and killing were caused by pyrimidine cyclobutane dimers. The caffeine inhibition repair studies performed were difficult to quantitate but did suggest either partial inhibition of a single repair pathway or alternate postreplication DNA repair pathways in Neurospora. No enhancement in killing was detected after UV irradiation when cells were grown on caffeine containing plates.
Mol Gen Genet 1982
PMID:Postreplication repair in Neurospora crassa. 621 89

Recombination frequencies for two sets of genetic markers of herpes simplex virus were determined in various host cells with and without ultraviolet irradiation of the virus. UV irradiation increased the recombination frequency in all the cell types studied in direct proportion to the unrepaired lethal damage. In human skin fibroblasts derived from a patient with xeroderma pigmentosum (XP) of complementation group A, a given dose of UV stimulated recombination more than that in fibroblasts from normal individuals. On the other hand, UV stimulation of HSV recombination was slightly less than normal in fibroblasts derived from a patient with a variant form XP and from an ataxia telangiectasia patient. Caffeine, an agent known to inhibit repair of UV damage, reduced recombination in most of the cell types studied and did not suppress the UV-induced increase in recombination. These findings suggest that for virus DNA with the same number of unrepaired UV-lesions, each of the tested cell types promoted HSV-recombination to an equivalent extent.
Mol Gen Genet 1980
PMID:Genetic recombination of herpes simplex virus, the role of the host cell and UV-irradiation of the virus. 624 34

Catecholamines (isoproterenol, adrenaline, and noradrenaline) elicited a small decrease in the resting potential of guinea-pig ventricular muscle cells depolarized by 27 mM K. This catecholamine-induced depolarization (CAD) was enhanced and often led to an automatic activity, when the membrane shunting conductance was reduced by application of 0.05 to 0.2 mM Ba. CAD was blocked by Mn (1 to 2 mM), verapamil (0.5 to 1 X 10(-5) M), and propranolol (0.1 to 1 X 10(-5) M), but not by phentolamine (10(-5) M). CAD did not develop when both Ca and Ba were absent in the bathing solution, but persisted when Sr was present. These results are consistent with the hypothesis that CAD was due at least partly to an increase in the slow channel conductance that was initiated by catecholamine/beta-receptor interaction. CAD was markedly enhanced at low temperatures (21 to 25 degrees C), and such was characterized by slow repolarization after drug withdrawal. Propranolol, when applied after catecholamine, exerted no appreciable effect on this slow repolarization. This beta-blocker abolished CAD at low temperature, if applied prior to catecholamine. Methylxanthines (2 to 5 mM caffeine or theophylline) produced a depolarization similar to that seen with CAD, and the rate of repolarization after drug withdrawal also slowed at low temperature. The slow repolarization of CAD at low temperature appeared to reflect a slowing in the postreceptor metabolic processes responsible for deactivation of the slow channel that was sensitive to beta-receptor stimulation.
J Mol Cell Cardiol 1983 Aug
PMID:Depolarization produced by catecholamines in guinea-pig ventricular muscle cells exposed to potassium-rich media and its dependence on temperature. 632 25

The addition of 0.1% caffeine to the plating medium markedly reduced the ozone-survival of the wild-type and the rad1 and rad6 mutants of Saccharomyces cerevisiae, whereas no effect was observed in the rad52 mutant. Since, in S. cerevisiae, caffeine has been reported to interfere with the recombinational repair pathway under the control of the RAD52 gene, these results support previous observations suggesting that this pathway is involved in the repair of ozone-induced DNA damage.
Mol Gen Genet 1984
PMID:Effect of caffeine on ozone-sensitivity in Saccharomyces cerevisiae. 638 92

The role of the sarcoplasmic reticulum in the regulation of cytosolic calcium is briefly reviewed. A method is described for monitoring calcium efflux from relatively large amounts of SR in a newly designed filtration apparatus using membrane filtration. Two phases of Ca2+ efflux from SR preloaded in the presence of oxalate were observed: an early exponential phase, followed by a phase of constant efflux. Changes in pH from 6.8 to 7.4 resulted in increased efflux. A change in the opposite direction resulted in an initial rapid increase in efflux before the expected decrease occurred. Caffeine (10 and 20 mM) caused increased efflux. Addition of 100 microM EGTA to the buffer resulted in major changes in the exponential phase but not in the phase of constant release, and potentiated the effect of caffeine. The method appears suitable for a variety of pharmacological studies in SR as well as other tissue fractions.
J Mol Cell Cardiol 1984 Feb
PMID:Ca2+ and the sarcoplasmic reticulum. 642 7

The abolition by caffeine of the arrhythmias induced by cardiotonic steroids was studied in canine Purkinje and ventricular muscle fibers and in guinea pig ventricular muscle perfused in vitro. Both the electrical and mechanical activity were recorded. The following results were obtained: (1) Caffeine (9 mM) quickly abolished the arrhythmias induced by strophanthidin (10(-6)M) in Purkinje fibers by inducing quiescence at a depolarized level; (2) A lower concentration of caffeine (3 mM) hastened the appearance of the arrhythmias by favoring the onset of spontaneous activity at a depolarized level but abolished the oscillatory potential at lower strophanthidin concentrations (2-5 X 10(-7)M); (3) Caffeine (9-10 mM) abolished the oscillatory potentials and after-contractions induced by cardiotonic steroids in ventricular muscle fibers; (4) Caffeine prevented the induction of oscillatory potentials and of arrhythmias by cardiotonic steroids; (5) In the presence of cardiotonic steroids and norepinephrine, the oscillatory potentials can induce fast discharge in myocardial fibers which is eliminated by caffeine; (6) High calcium and norepinephrine (singly or together) induce oscillatory potentials and after-contractions which are abolished by caffeine; (7) The elimination of the oscillatory potentials by caffeine in myocardial fibers is associated with the development of contracture. It is concluded that caffeine eliminates cardiac steroid-induced arrhythmias by quickly depolarizing Purkinje fibers and by eliminating the oscillatory potentials in myocardial fibers and (at suitable concentrations) also in Purkinje fibers.
J Mol Cell Cardiol 1984 Sep
PMID:On the mechanism by which caffeine abolishes the fast rhythms induced by cardiotonic steroids. 649 74

Myocardial compartmentation of calcium was investigated in the arterially perfused rabbit interventricular septum under conditions of augmented calcium uptake. Reduction of perfusate sodium concentration (100-36 mM [Na]0) produced the expected increased active force development and an increased myocardial calcium content that was inversely proportional to [Na]0. Caffeine was used to inhibit calcium uptake by the sarcoplasmic reticulum (SR) and to stimulate SR calcium release. The diastolic tension response to caffeine was also inversely proportional to [Na]0: at [Na]0 of 139 mM, 10 mM caffeine increased diastolic tension by 20%; whereas at 36 mM [Na]0 diastolic tension increased by 205%. The increase in diastolic tension in response to caffeine was considered a reflection of increased cytosolic calcium. The increase in diastolic tension with caffeine required that reduced [Na]0 be present at the time caffeine was administered. Caffeine sensitivity (measured by an increase in diastolic tension) and active force development declined to control levels within 3 minutes after the end of a 40 minute period of low [Na]0 perfusion despite the presence of an additional 1 mmole calcium per kg dry wt in the muscle at the 3 minute mark when caffeine was added. The results indicate that low [Na]0 perfusion induces an increment in myocardial calcium content, a major fraction of which is neither related directly to contractility nor involved in the response to caffeine.
J Mol Cell Cardiol 1984 Nov
PMID:Effects of low sodium perfusion on cardiac caffeine sensitivity and calcium uptake. 652 Aug 75

Calcium (Ca) exchange was studied under various perfusion conditions in monolayer myocardial culture and in the interventricular septum of the rabbit. In cultured cells perfused in HEPES buffered medium or in 10 mM phosphate (Pi), pH less than 7.2, 10 mM caffeine produced no change in 45Ca uptake rate. By contrast, increase of pH to 7.35 in the presence of 10 mM Pi caused 45Ca uptake rate to increase by more than two-fold when caffeine was added. Control 45Ca uptake (prior to caffeine) was markedly increased in 10 mM Pi, pH = 7.35 as compared to the two other perfusion conditions in the cultured cells. The same sequence of response of 47Ca uptake rate to caffeine was found in the rabbit septum, i.e. no increased uptake under HEPES or Pi, pH less than 7.2 perfusion, but significant increase under 10 mM Pi, pH 7.35 with development of progressive contracture only in the last case. Two other conditions produced sensitivity (both in 47Ca uptake and contracture) to caffeine in the septum. Preperfusion with ouabain in HEPES buffer increased caffeine sensitivity proportional to ouabain concentration (5 X 10(-7) to 10(-5) M) as did preperfusion with vanadate at low concentration (1 to 3 X 10(-6) M). The results suggest that activation of Ca uptake by the sarcoplasmic reticulum (SR) is dependent upon a threshold of cellular Ca and that a stable contractile state is possible in the absence of SR activation in both cultured cells and adult ventricular tissue.
J Mol Cell Cardiol 1983 Jul
PMID:Calcium compartmentalization in cultured and adult myocardium: activation of a caffeine-sensitive component. 655 45

Hypertonic solutions were found to exhibit both positive and negative inotropic effects on the contraction of the isolated atrial myocardium of bullfrog. The optimum tonicity for twitch potentiation was about 1.5 T. The mechanism for the positive inotropic action was investigated. The possibility of involvement of an increase in calcium influx during each action potential was excluded, since both the overshoot and the plateau of action potential were strongly depressed by perfusion of hypertonic solution. The effect on the time course of twitch potentiation was similar to that of muscle shrinkage, regardless of the type solute (sucrose, NaCl or LiCl) used for elevating the tonicity, except that excess sodium showed an initial rapid inhibitory phase of contraction. A marked post-rest potentiation was observed even after "zero" calcium perfusion, provided that the tonicity of the bathing medium was elevated previously. Potassium contracture occurred during the prolonged hypertonic perfusion in "zero" calcium condition. In addition, caffeine contracture was strongly augmented in hypertonic solution. The results suggest that an elevation in both the [Ca2+]i and amount of calcium bound intracellularly may play an important role in the positive inotropic action.
J Mol Cell Cardiol 1983 May
PMID:A study on the mechanism of twitch potentiation by hypertonic solution in the frog atrial muscle. 660 68


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