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)

Possible involvement of adenosine, as a secondary neurotransmitter, in opioid modulation of nociception and gastrointestinal function was investigated in mice. Inhibitory actions of theophylline, a nonselective adenosine receptor antagonist, were evaluated against effects evoked by opioid receptor-selective agonists administered at spinal or supraspinal sites. Intrathecal administration of theophylline significantly inhibited antinociceptive actions produced by intrathecal (i.th.) injections of morphine, [D-Ala2, NMPhe4, Gly-ol] enkephalin (DAMGO), [D-Pen2, D-Pen5] enkephalin (DPDPE) and beta-endorphin as measured with the warm water tail-flick assay. The rank order of rightward displacement of i.th. agonist dose-response curves by theophylline (i.th.) was DPDPE (greatest) > DAMGO > morphine > beta-endorphin. Theophylline was less effective as an inhibitor in the hot-plate assay. Additionally, i.th. administration of theophylline inhibited antinociceptive effects evoked by i.c.v. administration of opioids. The rank order of rightward displacement of dose-response curves after i.c.v. opioid administration was DAMGO (greatest) > beta-endorphin > morphine > DPDPE. In contrast to the effectiveness of theophylline administered i.th., theophylline coadministered i.c.v. with opioid agonists did not inhibit opioid-induced antinociception. Neither i.th. nor i.c.v. theophylline altered inhibitory effects on gastric emptying and gastrointestinal propulsion produced by i.th. or i.c.v. administration of selective opioid agonists. These data provide additional support for involvement of spinal adenosine as a secondary neurotransmitter in opioid antinociceptive processes associated with local spinal reflexes as well as in descending antinociceptive processes. Adenosine was not involved in modulation of opioid-activated gastrointestinal outflow pathways at either spinal or supraspinal levels.
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PMID:Involvement of adenosine in antinociception produced by spinal or supraspinal receptor-selective opioid agonists: dissociation from gastrointestinal effects in mice. 133 55

As shown by an increase in plasma corticosterone concentrations, adenosine administration stimulated pituitary-adrenocortical activity. This effect was prevented by dexamethasone (2 mg/kg i.p.). Added in vitro, adenosine reduced both adrenal basal and adrenocorticotropic hormone (ACTH)-stimulated corticosterone release, while it stimulated pituitary ACTH release. This ACTH response was blocked by dexamethasone but not by Tyr-somatostatin. Restraint stress increased adenosine content in the anterior pituitary, suggesting its possible involvement in hormonal stress response. Because the effect of adenosine on plasma corticosterone was still present in rats with a pharmacological block of the endogenous corticotropin-releasing factor release, we propose that adenosine is involved in the regulation of adrenocortical secretion at the level of the anterior pituitary and that this role is exerted through an interaction with a stimulatory adenosine receptor.
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PMID:Adenosine and pituitary-adrenocortical axis activity in the rat. 281 76

It has been previously demonstrated that activation of A1 adenosine receptors in frog melanotrophs causes inhibition of spontaneous action potential discharges and alpha-melanocyte-stimulating hormone secretion. In the present study, we have investigated the effect of adenosine on high-voltage-activated (HVA) calcium currents in cultured melanotrophs, using the whole-cell variant of the patch-clamp technique with barium as a charge carrier. Adenosine and the specific A1 adenosine receptor agonist R-PIA (50 microM each) produced a decrease of the amplitude of the barium current, while the selective A2 adenosine receptor agonist CGS 21680 did not affect the current. The inhibitory effect of R-PIA was observed throughout the activation range of the current, with stronger responses at more positive potentials. R-PIA inhibited both the L- and N-type components of the current, the effect on the N-component being two-fold higher than on the L-component. The inhibitory effect of R-PIA was rendered irreversible by addition of GTP gamma S (100 microM) to the intracellular solution. Pre-treatment of the cells with pertussis toxin (1 microgram/ml; 12 h) totally abolished the effect of R-PIA on the HVA calcium channels. Conversely, addition of a high concentration of cAMP (100 microM) together with the phosphodiesterase inhibitor IBMX (100 microM) to the intracellular solution did not modify the effect of R-PIA on the current. It is concluded that, in frog melanotrophs, adenosine induces inhibition of L- and N-calcium currents and that this effect is mediated by a pertussis toxin-sensitive G protein. Our data also indicate that the inhibitory effect of adenosine on the calcium currents is not mediated by inhibition of adenylyl cyclase.
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PMID:Adenosine inhibits L- and N-type calcium channels in pituitary melanotrophs. Evidence for the involvement of a G protein in calcium channel gating. 886 54

A previous study reported that beta-endorphin and morphine administered supraspinally produce antinociception by activating different descending pain inhibitory systems. The present study was designed to investigate the blocking effects of A1 or A2 adenosine receptors in the spinal cord on antinociception induced by supraspinally administered mu- and epsilon-opioid receptor agonists. The effects of 1,3-dipropyl-8-(2-amino-4-chloro-phenyl)-xanthine (PACPX; an A1 adenosine receptor antagonist) or 3,7-dimethyl-1-propargylxanthine (DMPX; an A2 adenosine receptor antagonist) on the antinociception induced by morphine (a mu-opioid receptor agonist) or beta-endorphin (an epsilon-opioid receptor agonist) administered intracerebroventricularly (i.c.v.) were studied. The antinociception was assayed by the tail-flick test. DMPX at doses of 1-40 micrograms (which administered intrathecally alone did not affect the latencies of tail-flick thresholds), attenuated dose-dependently the inhibition of the tail-flick response induced by i.c.v. administered morphine (0.5 microgram) or beta-endorphin (1 microgram). PACPX at doses of 1-40 micrograms (which administered intrathecally alone did not affect the latencies of tail-flick thresholds), attenuated dose-dependently the inhibition of the tail-flick response induced by i.c.v. administered beta-endorphin but not morphine. These results suggest that A2 but not A1 adenosine receptors in the spinal cord may be involved in the antinociception induced by supraspinally administered morphine, while the antinociception induced by supraspinally administered beta-endorphin appears to be mediated by spinal A1 and A2 adenosine receptors. These results support the hypothesis that morphine and beta-endorphin administered supraspinally produce antinociception by different neuronal mechanisms.
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PMID:Differential effects of adenosine receptor antagonists injected intrathecally on antinociception induced by morphine and beta-endorphin administered intracerebroventricularly in the mouse. 930 21

Recently we have shown that the cAMP system is involved in ethanol-regulated beta-endorphin (beta-EP) release from rat hypothalamic neurons in primary cultures. The cascade of events that leads to activation of cAMP following ethanol treatment in hypothalamic beta-EP neurons is not apparent. In this study the role of adenosine, a cAMP regulator, in ethanol-regulated beta-EP release was determined by measuring the cellular incorporation of [3H]adenosine, intracellular cAMP levels and media immunoreactive (IR) beta-EP levels in cultures of rat hypothalamic cells following ethanol treatments in the presence and absence of an adenosine agonist and antagonist. Acute exposure to a 50 mM dose of ethanol for a period of 1 h increased media levels of IR-beta-EP and cellular contents of cAMP, but the ethanol treatment decreased [3H]adenosine uptake. Constant exposure to a 50 mM dose of ethanol for a period of 48 h, failed to alter media levels of IR-beta-EP, cell content of cAMP and [3H]adenosine uptake. The media level of IR-beta-EP was elevated following treatment with adenosine receptor agonist phenyl-isopropyl adenosine (PIA) and was reduced following treatment with adenosine receptor antagonist isobutylmethylxanthine (IBMX) or with adenosine uptake inhibitor adenosine deaminase. The level of cellular cAMP was also increased by PIA but was decreased by IBMX and adenosine deaminase. The stimulatory actions of the adenosine agonist PIA on IR-beta-EP release and on cAMP production were potentiated by simultaneous incubation with ethanol for 1 h. However, chronic ethanol exposure reduced PIA-induced IR-beta-EP release and cAMP production. Additionally, both IBMX and adenosine deaminase reduced ethanol-induced IR-beta-EP release and cAMP levels. These results suggest that ethanol inhibits adenosine uptake in IR-beta-EP neurons in the hypothalamus, thereby increasing extracellular levels of adenosine and leading to activation of membrane adenosine receptors, cAMP production and IR-beta-EP secretion from these neurons. Chronic ethanol desensitizes the adenosine-regulated cAMP production and IR-beta-EP release from hypothalamic neurons.
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PMID:Effects of ethanol on basal and adenosine-induced increases in beta-endorphin release and intracellular cAMP levels in hypothalamic cells. 1009 49