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)

Human beta-endorphin 1-31 (beta-END) stimulated low-Km GTPase activity in a concentration-dependent and saturable manner in membranes prepared from the delta opioid receptor-containing hybrid cell line NG108-15 and from the mu opioid receptor-enriched human neuroblastoma cell line SK-N-SH. Naloxone and the delta-selective antagonist, ICI 174,864, blocked the stimulation of the GTPase activity produced by beta-END in NG108-15 cell membranes, whereas only naloxone inhibited the beta-END-induced stimulation in SK-N-SH cell membranes, suggesting that beta-END was acting through both mu and delta opioid receptors. Treatment of the cells with Bordetella pertussis toxin before the preparation of membranes blocked the stimulation of low-Km GTPase by beta-END in both cell lines. Activation of NG108-15 and SK-N-SH low-Km GTPase by beta-END was sodium-dependent, and lithium and potassium were poor promoters of this activation. These results demonstrate that beta-END stimulates the interaction of both mu and delta opioid receptors with B. pertussis toxin-sensitive G-proteins in SK-N-SH and NG108-15 cell membranes, respectively.
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PMID:Effects of beta-endorphin on mu and delta opioid receptor-coupled G-protein activity: low-Km GTPase studies. 132 14

Morphine inhibited the adenylate cyclase activity of the crude synaptosomal fraction of the rat caudate nucleus in the presence of BTP, GDP, Gpp(NH)p or ITP. The purine nucleotides themselves had an inhibitory action on the enzyme. Beta-endorphin and Met-enkephalin also inhibited the enzyme in the presence of GTP. The GTP-dependent in inhibitory action of morphine was blocked by naloxone. Various opiates and opioid peptides inhibited the enzyme by up to approximately 20 per cent in the presence of GTP. The relative potency was in higher order of levorphanol greater than beta-endorphin greater than Met-enkephalin greater than morphine greater than pentazocine. Levorphanol was about 50,000 times as potent as its biologically inactive enantiomer, dextrorphan. Morphine enhanced the inhibitory actions of GTP and GTPase-resistant Gpp(NH)p on the adenylate cyclase activity. These results suggest that GTP plays an important role in the regulation of adenylate cyclase activity in the rat caudate nucleus and that the occupation of opiate receptor by agonists inhibits the enzyme through an actual increase in the inhibitory action of GTP, rather than a suppression of the enzymatic degradation of GTP.
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PMID:Inhibition of adenylate cyclase by GTP and its modulation by opiate receptor in rat caudate nucleus. 627 23

Intracerebroventricular (i.c.v.) administration to mice of IgGs raised against alpha subunits of Gi2 or Gx/z transducer proteins lessened the activation of low Km GTPase induced by morphine, DAMGO and DADLE in P2 membranes from mouse periaqueductal grey matter (PAG). In mice injected with anti Gi2 alpha, DADLE, DPDPE and [D-Ala2] Deltorphin II, but not beta-endorphin-(1-31), antagonized the analgesic activity of morphine. Conversely, following anti Gx/z alpha, morphine antagonized the antinociceptive potency of DADLE. It is concluded that opioids display diverse efficacy at mu-Gi2 and mu-Gx/z complexes to produce supraspinal analgesia in mice.
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PMID:Dissimilar efficacy of opioids to produce mu-mediated analgesia: role of Gx/z and Gi2 transducer proteins. 791 94

In mice whose Gi/o-protein function had been impaired by antisense 'knock-down' or pertussis toxin treatment, i.c.v. injection of myr+-Gi/o alpha subunits restored the effectiveness of beta-endorphin, morphine, DPDPE, clonidine and neurotensin to produce antinociception. Myr+-G alpha subunits of the class of G-proteins actually impaired were more effective than unlike but related myr+-G alpha subunits. Selectivity was noted in that only exogenous myr+-G alpha subunits affected (enhanced) the activity of agonists in G alpha-deficient signalling systems. This treatment had little effect on agonist potency when the impairment resided at the receptor level. The potential of the opioids, clonidine and R-PIA to increase G alpha-related in vitro hydrolysis of GTP was also re-established after injecting myr+-Gi2 alpha subunits into Gi2-knocked-down mice. Myr+-Gi2 alpha subunits pre-incubated with GTPgammaS or GDPbetaS before i.c.v. injection did not improve the activity of agonists in vivo (antinociception) or in vitro (regulation of low Km GTPase). After impairing the function of PKCbeta1 by antisense treatment or with the inhibitor H7, the effect of myr+-G alpha subunits on agonist potency was prevented. Electron microscope analysis showed the entry of gold-conjugated myr+-G alpha subunits into neural cells. These particles were found in the cytoplasm, associated with the plasma membranes of different neuronal processes and also in synaptic junctions. In cultured neurons and astrocytes myr+-Gi2 alpha-associated fluorescence was internalised in a dose-dependent manner and distributed in the plasma membrane and cytosol, as well as in nuclei of dividing astrocytes. Thus, G alpha subunits in CSF enter into neurons and functionally couple to the receptor-triggered signalling cascade. As G-proteins have been implicated in the pathophysiology of several neural disorders, this finding may be valuable in the therapy of such dysfunctions.
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PMID:Myr+-Gi2 alpha and Go alpha subunits restore the efficacy of opioids, clonidine and neurotensin giving rise to antinociception in G-protein knock-down mice. 1060 81

This paper reports that regulators of G-protein signalling (RGS) proteins modulate the timing and amplitude of opioid signals by a push-pull mechanism. This is achieved without noticeable changes in the binding properties of opioids, e.g. beta-endorphin to mu-opioid receptors. The expression of RGS proteins was reduced by blocking their mRNA with antisense oligodeoxynucleotides (ODN). Knock down of RGS2 or RGS3 diminished morphine and beta-endorphin analgesia, whereas that of RGS9 or RGS12 enhanced this activity. In mice with impaired RGS9, but not impaired RGS2, the potency and, in particular, the duration of opioid antinociception increased. Further, the animals did not exhibit acute tolerance generated by a single and efficacious dose of morphine, nor did they develop tolerance after a daily i.c.v. injection of the opioid for 4 days. In a model of sustained morphine treatment, the impairment of RGS9 proteins facilitated increases in the response to the delivered opioid. This was only effective for 2--3 h after the subcutaneous implantation of an oily morphine pellet; later, tolerance developed. To reduce the impact of the chronic morphine acting on opioid receptors, other RGS proteins presumably substitute the GTPase-activating function of RGS9 on morphine-activated G-alpha-GTP subunits. The desensitization of mu-opioid receptors appears to be a cell membrane-limited process facilitated by RGS9's sequestering of agonist-segregated G alpha subunits.
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PMID:RGS9 proteins facilitate acute tolerance to mu-opioid effects. 1120 15

The purpose of this study was to investigate the metabolism of Adenosine triphosphate (ATP) in skeletal muscle resistance arterioles and to determine whether this metabolism is altered during the rapid growth phase of the rat. We attempted to quantify ATP metabolism in gastrocnemius first-order arterioles from 8-, 10-, and 12-week-old rats. We measured ATP metabolism using an ATPase/GTPase assay with whole vessel segments as well as using a real-time adenosine biosensor following electric field stimulation. Our first method of measuring ATP metabolism allowed us to measure the amount of free phosphate produced with ATP as a substrate. When ecto-nucleotidase activity was inhibited by ARL67156, pyridoxal phosphate-6-azophenly-2', 4'-disulfonic acid (PPADS), or suramin prior to adding ATP, we found that the rate of phosphate production was significantly reduced by 27%, 21%, and 22%, respectively (P < 0.05). Our second method of measuring ATP metabolism allowed us to measure the amount of adenosine produced following electric field stimulation of the arteriole with and without nucleotidase inhibitors. Surprisingly, we found that adenosine overflow was not attenuated by nucleotidase inhibitors. We concluded that ecto-phosphodieterase/phyrophophatase (E-NPP), ecto-diadenosine polyphosphatase (ApnA), NTPDase1 and 2, and E5NT may be present on the gastrocnemius 1A arteriole and do play a role in ATP metabolism. Between the ages of 8 weeks and 12 weeks, however, overall ATP metabolism may not change.
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PMID:ATP metabolism in skeletal muscle arterioles. 2474 86