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)

When rats were exposed to immobilization stress for 1-12 h, gastric lesions did not occur at 1-6 h but did at 12 h of immobilization. Exogenous adenosine increased stress-induced gastric lesions, and dipyridamole, a blocker of adenosine uptake, potentiated the action of adenosine. The selective adenosine A1-receptor stimulants N6-cyclohexyl adenosine (CHA) and N6-(L-phenylisopropyl) adenosine (L-PIA) produced gastric lesions even in non-stressed state and markedly potentiated in dose- and time-dependent manner in stressed state. The stimulatory effect of N6-(D-phenylisopropyl) adenosine (D-PIA) on ulceration was weaker than that of CHA or L-PIA. Furthermore, intracerebral ventricular (i.c.v.) injection of adenosine or adenosine analogues produced the most rapid and most potent exacerbation of stress-induced gastric lesions relative to those induced with subcutaneous (s.c.) injection. The stress lesions enhanced by CHA were not affected by phentolamine, yohimbine, prazosin, naloxone and cholecystokinin (CCK8) but were inhibited by caffeine, clonidine, morphine and beta-endorphin. The inhibitory effect of clonidine was not antagonized by yohimbine or prazosin. The inhibition by morphine was selectively antagonized by exogenous CCK8 as well as naloxone. These results suggest that endogenous adenosine is tonically active in stress lesion formation which is modulated by opiate systems. Clonidine as well as caffeine may function as a purinoceptor antagonist, and it seems unlikely that the inhibitory effect of clonidine on stress ulcer is due to activation of alpha-adrenoceptors.
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PMID:Development of stress-induced gastric lesions involves central adenosine A1-receptor stimulation. 299 4

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

Our laboratory demonstrated that adenosine inhibits the activation of adenylyl cyclase and the secretion of the alpha-melanocyte-stimulating hormone (alpha-MSH) from the intermediate lobe of the frog pituitary. This paper showed the bioelectric effects induced by adenosine, the ionic conductances modulated by adenosine, and the possible involvement of intracellular messengers, indicated the mechanism by which adenosine controls the secretion of alpha-MSH. The results show that adenosine acting on A1 adenosine receptor subtype reduced the Ca2+ influx necessary for the secretion, through 4 distinct mechanisms: 1) a hyperpolarization resulting from the activation of a voltage-insensitive K+ conductance, 2) a reduction of the duration of spontaneous action potentials due to an increase of the outward delayed rectifyer K+ current (lk), 3) a diminution of the cellular excitability by an activation of the transient outward K+ current (lA), and 4) an inhibition of the L- and N-type Ca2+ currents, with a predominant action on the N-type component. Cell dialysis with GTP gamma S rendered irreversible the effects of adenosine on the K+ conductances and Ca2+ channels, whereas PTX pretreatment totally abolished the response to adenosine, suggesting all bioelectric effects of adenosine were mediated by pertussis toxin-sensitive G proteins. Whether the implicated G proteins regulate the K+ and Ca2+ channels by tight-coupling or via a second-messenger system remains to be solved. With our results, the involvement of adenylyl cyclase can be excluded because addition of cAMP and IBMX, an inhibitor of phosphodiesterases, in the intracellular solution, or application of dibutyryl cAMP in the extracellular solution did not modify the adenosine-induced responses.
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PMID:Patch clamp study on mechanism of adenosine-induced inhibitory effects in frog pituitary melanotrophs. 986 55

Adenosine can reduce pain and allodynia in animals and man, probably via spinal adenosine A1 receptors. In the present study, we investigate the distribution of the adenosine A1 receptor in the rat spinal cord dorsal horn using immunohistochemistry, in situ hybridization, radioligand binding, and confocal microscopy. In the lumbar cord dorsal horn, dense immunoreactivity was seen in the inner part of lamina II. This was unaltered by dorsal root section or thoracic cord hemisection. Confocal microscopy of the dorsal horn revealed close anatomical relationships but no or only minor overlap between A1 receptors and immunoreactivity for markers associated with primary afferent central endings: calcitonin gene-related peptide, or isolectin B4, or with neuronal subpopulations: mu-opioid receptor, neuronal nitric oxide synthase, met-enkephalin, parvalbumin, or protein kinase Cgamma, or with glial cells: glial fibrillary acidic protein. A few adenosine A1 receptor positive structures were double-labeled with alpha-amino-3-hydroxy-5-methyl-4-isoaxolepropionic acid glutamate receptor subunits 1 and 2/3. The results indicate that most of the adenosine A1 receptors in the dorsal horn are located in inner lamina II postsynaptic neuronal cell bodies and processes whose functional and neurochemical identity is so far unknown. Many adenosine A1 receptor positive structures are in close contact with isolectin B4 positive C-fiber primary afferents and/or postsynaptic structures containing components of importance for the modulation of nociceptive information.
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PMID:Distribution of antinociceptive adenosine A1 receptors in the spinal cord dorsal horn, and relationship to primary afferents and neuronal subpopulations. 1458 Sep 41