Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intracellular calcium mobilization is an important early event involved in T cell activation. The endogenous opioid peptide beta-endorphin is known to modulate immune functions that depend on T cell activation, therefore its effect on intracellular calcium mobilization was investigated. The intracellular calcium concentration ([Ca2+]i) of T cell-enriched splenocytes was measured by flow cytofluorometric analysis using the calcium-sensitive dye, Fluo-3. By gating on the T cell marker, Thy-1, a 95%-pure population of T cells was identified for study. Cells preincubated with beta-endorphin showed significantly enhanced [Ca2+]i responses to the mitogen, Concanavalin A (Con A). This was detectable with concentrations of beta-endorphin as low as 10(-13) M; maximal enhancement required 10(-10) to 10(-9) M doses. The efficacy of beta-endorphin was dependent on the duration of pretreatment. beta-Endorphin amplified the Con A-induced increase in [Ca2+]i by reducing the lag time for the response to Con A and by increasing the mean [Ca2+]i of the cells. N-Ac-beta-endorphin, which shows minimal potency at neuronal opiate receptors, was unable to substitute for beta-endorphin. Naltrindole, a highly selective delta opiate receptor antagonist, inhibited the action of beta-endorphin, whereas a selective mu opiate receptor antagonist was ineffective. Although less potent than beta-endorphin, the delta opiate receptor agonist D-Ala2-D-Leu5-enkephalin also significantly enhanced [Ca2+]i responses. In summary, concentrations of beta-endorphin, within the physiological range found in the systemic circulation, modulate the increase in T cell [Ca2+]i induced by Con A. Both the efficacy of D-Ala2-D-Leu5-enkephalin alone and the antagonism of beta-endorphin by naltrindole suggest that a delta-type opiate receptor may mediate these effects.
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PMID:Beta-endorphin enhances Concanavalin-A-stimulated calcium mobilization by murine splenic T cells. 875 65

The factors regulating Ca2+ transport by isolated sarcoplasmic reticulum (SR) vesicles have been studied using the fluorescent indicator Fluo-3 to monitor extravesicular free [Ca2+]. ATP, in the presence of 5 mM oxalate, which clamps intravesicular [Ca2+] at approximately 10 microM, induced a rapid decline in Fluo-3 fluorescence to reach a limiting steady state level. This corresponds to a residual medium [Ca2+] of 100 to 200 nM, and has been defined as [Ca2+]lim, whilst thermodynamic considerations predict a level of less than 1 nM. This value is similar to that measured in intact muscle with Ca2+ fluophores, where it is presumed that sarcoplasmic free [Ca2+] is a balance between pump and leaks. Fluorescence of Fluo-3 at [Ca2+]lim was decreased 70% to 80% by histidine, imidazole and cysteine. The K0.5 value for histidine was 3 mM, suggesting that residual [Ca2+]lim fluorescence is due to Zn2+. The level of Zn2+ in preparations of SR vesicles, measured by atomic absorption, was 0.47+/-0.04 nmol/mg, corresponding to 0.1 mol per mol Ca-ATPase. This is in agreement with findings of Papp et al. (Arch. Biochem. Biophys., 243 (1985) 254-263). Histidine, 20 mM, included in the buffer, gave a corrected value for [Ca2+]lim of 49+/-1.8 nM, which is still higher than predicted on thermodynamic grounds. A possible 'pump/leak' mechanism was tested by the effects of varying active Ca2+ transport 1 to 2 orders with temperature and pH. [Ca2+]lim remained relatively constant under these conditions. Alternate substrates acetyl phosphate and p-NPP gave similar [Ca2+]lim levels even though the latter substrate supported transport 500-fold slower than with ATP. In fact, [Ca2+]lim was lower with 10 mM p-NPP than with 5 mM ATP. The magnitude of passive efflux from Ca-oxalate loaded SR during the steady state of [Ca2+]lim was estimated by the unidirectional flux of 45Ca2+, and directly, following depletion of ATP, by measuring release of 40Ca2+, and was 0.02% of Vmax. Constant infusion of CaCl2 at [Ca2+]lim resulted in a new steady state, in which active transport into SR vesicles balances the infusion rate. Varying infusion rates allows determination of [Ca2+]-dependence of transport in the absence of chelating agents. Parameters of non-linear regression were Vmax=853 nmol/min per mg, K0.5(Ca)=279 nM, and nH(Ca)=1.89. Since conditions employed in this study are similar to those in the sarcoplasm of relaxed muscle, it is suggested that histidine, added to media in studies of intracellular Ca2+ transients, and in the relaxed state, will minimise contribution of Zn2+ to fluophore fluorescence, since it occurs at levels predicted in this study to cause significant overestimation of cytoplasmic free [Ca2+] in the relaxed state. Similar precautions may apply to non-muscle cells as well. This study also suggests that [Ca2+]lim in the resting state is a characteristic feature of Ca2+ pump function, rather than a balance between active transport and passive leakage pathways.
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PMID:Regulation of Ca2+ transport by sarcoplasmic reticulum Ca2+-ATPase at limiting [Ca2+]. 1020 10

The mechanisms of toxicity of cadmium (Cd(2+)) in adrenal steroidogenesis were investigated in vitro in adrenocortical cells of rainbow trout (Oncorhynchus mykiss). Toxicity of Cd(2+) was increased in absence of extracellular Ca(2+), but was prevented in Ca(2+)-supplemented medium. Pretreatment of cells with BAY K8644 (BAY), an agonist of voltage-dependent calcium channels, increased the Cd(2+)-mediated inhibition of ACTH-stimulated secretion but not pregnenolone (PREG)-stimulated secretion. Nicardipine, an antagonist of voltage-dependent calcium channels, also increased the inhibition of adrenocorticotropic hormone (ACTH)-stimulated secretion by Cd(2+). These results suggest that opening of voltage-dependent calcium channels with BAY may allow Cd(2+) entry at the same time as calcium, thus increasing toxicity of Cd(2+), however voltage-dependent calcium channels may not be the only way of entry into adrenocortical cells. The influx of Cd(2+), measured as intracellular Cd(2+) using Fluo-3 in PREG-stimulated adrenocortical cells, was significantly enhanced by the stimulation. These results suggest that the deleterious effect of Cd(2+) on cortisol steroidogenesis may be enhanced when the endocrine stress response is triggered.
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PMID:Role of calcium channels in cadmium-induced disruption of cortisol synthesis in rainbow trout (Oncorhynchus mykiss). 1695 44