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)

The experiments were designed to determine the role of pertussis toxin-(PTX) sensitive G-proteins Gi/Go in the brain and spinal cord in antinociception induced by epsilon-opioid receptor agonist beta-endorphin (beta-EP) and mu-opioid receptor agonist morphine. The effects of intracerebroventricular (i.c.v.) or intrathecal (i.t.) pretreatment with PTX on antinociception induced by morphine, beta-endorphin (beta-EP) and other selective opioid receptor agonists given i.c.v. or i.t. were studied in male ICR mice. Antinociception was assessed by the tail-flick and hot-plate tests. An i.c.v. pretreatment with PTX (0.5 microgram) caused a time- and dose-dependent attenuation of the tail-flick and hot-plate inhibition induced by i.c.v.-challenged morphine-induced antinociception. However, the same pretreatment with PTX did not affect the antinociception induced by i.c.v.-administered beta-EP. The tail-flick and hot-plate inhibition induced by selective mu-, delta- and kappa-opioid receptor agonist, DAMGO, [D-Ala2]deltorphin II and U50,488H, respectively, given i.c.v. was also attenuated by the i.c.v. pretreatment with PTX. An i.t. pretreatment with PTX (0.5 microgram) blocked markedly the tail-flick inhibition induced by morphine and beta-EP given i.c.v. However, the same treatment did not affect the hot-plate inhibition induced by beta-EP and attenuated, to a lesser degree, the hot-plate inhibition induced by morphine given i.c.v. An i.t. pretreatment with PTX blocked the tail-flick inhibition induced by selective delta 2-, alpha 2 and 5-HT receptor agonist [D-Ala2]deltorphin, norepinephrine and 5-HT, respectively, given i.t. Our results indicate that the antinociception induced by mu-, delta-, kappa-opioid receptor agonists given supraspinally is mediated by respectively opioid receptors that are coupled to PTX-sensitive Gi/Go proteins at the supraspinal sites and subsequently mediated by the activation of PTX-sensitive Gi/Go coupled receptors in the spinal cord. However, the antinociception induced by beta-EP given supraspinally is mediated by the PTX-resistant epsilon-opioid receptors at the supraspinal sites and subsequently activation of the delta 2-opioid receptors in the spinal cord that is sensitive to the pretreatment with PTX.
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PMID:Pretreatment with pertussis toxin differentially modulates morphine- and beta-endorphin-induced antinociception in the mouse. 885 73

Bovine adrenal cortical cells (BAC) express corticotropin (ACTH) and angiotensin II (AngII) receptors (AT1 subtype), which are coupled to adenylate cyclase and phosphoinositide pathways, respectively. The coupling of AT1 to phosphoinositide breakdown is mainly pertussis toxin-insensitive suggesting that this receptor is coupled to Gaeq/Gae11. In the present work we have demonstrated that BAC express G alpha q and G alpha 11 mRNA and proteins, and their variation during culture as well as their regulation by ACTH and AngII is different. ACTH enhanced G alpha q mRNA levels mainly by increasing the transcription rate. In addition, ACTH increased both G alpha q and G alpha 11 proteins without changing their half-lives. In contrast, AngII reduced both G alpha q mRNA and protein and increased G alpha 11 mRNA but not G alpha 11 protein. The decrease of G alpha q mRNA levels was mainly due to a marked reduction of its half-life. These changes in G alpha q/G alpha 11 proteins induced by both hormones were associated with an enhanced AngII-induced inositol phosphate accumulation, more marked after stimulation with ACTH than after AngII pretreatment. In summary, the present results demonstrated that BAC express both G alpha q and G alpha 11 and their regulations are different and in contrast to other cell types these regulations do not involve changes in the half-life of G alpha q/G alpha 11 proteins.
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PMID:Expression and regulation of G alpha q and G alpha 11 mRNAs and proteins in bovine adrenal cells. 886 67

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

Bovine adrenal zona fasciculata (AZF) cells express a noninactivating K+ current (IAC) that is inhibited by adrenocorticotropic hormone (ACTH) at picomolar concentrations. Inhibition of IAC may be a critical step in depolarization-dependent Ca2+ entry leading to cortisol secretion. In whole-cell patch clamp recordings from AZF cells, we have characterized properties of IAC and the signalling pathway by which ACTH inhibits this current. IAC was identified as a voltage-gated, outwardly rectifying, K(+)-selective current whose inhibition by ACTH required activation of a pertussis toxin-insensitive GTP binding protein. IAC was selectively inhibited by the cAMP analogue 8-(4-chlorophenylthio)-adenosine 3':5'-cyclic monophosphate (8-pcpt-cAMP) with an IC50 of 160 microM. The adenylate cyclase activator forskolin (2.5 microM) also reduced IAC by 92 +/- 4.7%. Inhibition of IAC by ACTH, 8-pcpt-cAMP and forskolin was not prevented by the cAMP-dependent protein kinase inhibitors H-89 (5 microM), cAMP-dependent protein kinase inhibitor peptide (PKI[5-24]) (2 microM), (Rp)-cAMPS (500 microM), or by the nonspecific protein kinase inhibitor staurosporine (100 nM) applied externally or intracellularly through the patch pipette. At the same concentrations, these kinase inhibitors abolished 8-pcpt-cAMP-stimulated A-kinase activity in AZF cell extracts. In intact AZF cells, 8-pcpt-cAMP activated A-kinase with an EC50 of 77 nM, a concentration 2,000-fold lower than that inhibiting IAC half maximally. The active catalytic subunit of A-kinase applied intracellularly through the recording pipette failed to alter functional expression of IAC. The inhibition of IAC by ACTH and 8-pcpt-cAMP was eliminated by substituting the nonhydrolyzable ATP analogue AMP-PNP for ATP in the pipette solution. Penfluridol, an antagonist of T-type Ca2+ channels inhibited 8-pcpt-cAMP-induced cortisol secretion with an IC50 of 0.33 microM, a concentration that effectively blocks Ca2+ channel in these cells. These results demonstrate that IAC is a K(+)-selective current whose gating is controlled by an unusual combination of metabolic factors and membrane voltage. IAC may be the first example of an ionic current that is inhibited by cAMP through an A-kinase-independent mechanism. The A-kinase-independent inhibition of IAC by ACTH and cAMP through a mechanism requiring ATP hydrolysis appears to be a unique form of channel modulation. These findings suggest a model for cortisol secretion wherein cAMP combines with two separate effectors to activate parallel steroidogenic signalling pathways. These include the traditional A-kinase-dependent signalling cascade and a novel pathway wherein cAMP binding to IAC K+ channels leads to membrane depolarization and Ca2+ entry. The simultaneous activation of A-kinase- and Ca(2+)-dependent pathways produces the full steroidogenic response.
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PMID:Adrenocorticotropic hormone and cAMP inhibit noninactivating K+ current in adrenocortical cells by an A-kinase-independent mechanism requiring ATP hydrolysis. 889 75

Bovine chromaffin cells possess a mixture of high-voltage-activated Ca2+ channel subtypes: L-type, dihydropyridine-sensitive channels, and N-, P- and Q-types, omega-conotoxin MVIIC-sensitive channels. In these cells, we studied the reversible, naloxone-antagonized inhibition of Ba2+ currents by the opioid agonist met-enkephalin (IC50 = 272 nM). This inhibition could be resolved into a voltage-dependent and a voltage-independent component. The first was revealed by its slow Ba2+ current activation kinetics at 0 mV and by the current facilitation induced by short prepulses to +90 mV. The second was estimated as the residual inhibition persisting after the facilitation protocol. The two inhibitory components varied markedly from cell to cell and each contributed to about half of the total inhibition. Replacement of internal GTP by GDP-beta-S or cell pretreatment with pertussis toxin completely abolished the voltage-dependent inhibition by opioids, partially preserving the voltage-independent component. The opioid-induced inhibition was not selective for any Ca2+ channel subtype, being not prevented after the addition of specific Ca2+ channel antagonists. However, when separately analysing the contribution of each channel type to the voltage-dependent and voltage-independent modulation, a clear-cut distinction could be achieved. The voltage-independent inhibition was effective on all Ca2+ channel subtypes but predominantly on L-type Ca2+ channels. The voltage-dependent process was abolished by omega-conotoxin-MVIIC, but unaffected by nifedipine, and was thus sharply restricted to non-L-type channels (N-, P- and Q-types). Our data suggest a functionally distinct opioid receptor-mediated modulation of L- and non-L-type channels, i.e. of the two channel classes sharing major control of catecholamine secretion from bovine chromaffin cells.
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PMID:Opioid inhibition of Ca2+ channel subtypes in bovine chromaffin cells: selectivity of action and voltage-dependence. 892 Dec 48

We studied the effect of the adenylate cyclase activator forskolin, of protein kinase C-activating phorbol esters and of prolonged preganglionic input activation on the inhibitory response of the perfused superior cervical ganglion of the cat to exogenous met-enkephalin (Met-ENK). Met-ENK inhibited, in a concentration-dependent manner, the postganglionic compound action potential evoked by cervical sympathetic trunk stimulation. The inhibition was reversible, was blocked by naloxone as well as by pertussis toxin and showed no homologous desensitization in the concentration range 0.01-10 microM. Pretreatment of the ganglion with 4 beta-phorbol 12,13-dibutyrate or 4 beta-phorbol 12,13-diacetate depressed the Met-ENK response for several hours, while pretreatment with forskolin had no effect. This action of phorbol esters was prevented by the protein kinase inhibitor H-7 but not by the calmodulin antagonist W-7 or the protein kinase A inhibitor HA 1004 and was calcium-dependent. Recovery of the response from the depression produced by phorbol esters was not affected by a protein synthesis inhibitor. A 40 Hz 20 min stimulus train to the cervical sympathetic trunk mimicked the effect of phorbol esters, depressing for several hours the inhibition produced by Met-ENK. Stimulus trains of duration shorter than 5 min or frequency lower than 5 Hz were ineffective. This effect of prolonged preganglionic stimulation occurred even when the stimulus train was delivered during complete block of nicotinic and muscarinic ganglionic transmission but was lost when the stimulus train was delivered during perfusion with calcium-free Krebs. The protein kinase inhibitor H-7 prevented the depression of the Met-ENK response by the train, while W-7 and HA 1004 had no effect. These findings suggest that, in the superior cervical ganglion of the cat, a kinase, activated by phorbol esters and inhibited by H-7, exerts a long-term control of the ganglion cell responsiveness to opiate receptor activation. A similar mechanism can be synaptically activated by a non-cholinergic transmitter, released by the preganglionic axons during prolonged, high frequency, activity.
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PMID:Long-term depression of a sympathetic ganglionic response to opioids by prolonged synaptic activity and by phorbol esters. 896 46

The ultra-potent opioid analgesic, etorphine, elicits naloxone-reversible, dose-dependent inhibitory effects, i.e., shortening of the action potential duration (APD) of naive and chronic morphine-treated sensory dorsal root ganglion (DRG) neurons, even at low (pM-nM) concentrations. In contrast, morphine and most other opioid agonists elicit excitatory effects, i.e., APD prolongation, at these low opioid concentrations, require much higher (ca. 0.1-1 microM) concentrations to shorten the APD of naive neurons, and evoke only excitatory effects on chronic morphine-treated cells even at high > 1-10 microM concentrations. In addition to the potent agonist action of etorphine at mu-, delta- and kappa-inhibitory opioid receptors in vivo and on DRG neurons in culture, this opioid has also been shown to be a potent antagonist of excitatory mu-, delta- and kappa-receptor functions in naive and chronic morphine-treated DRG neurons. The present study demonstrates that the potent inhibitory APD-shortening effects of etorphine still occur in DRG neurons tested in the presence of a mixture of selective antagonists that blocks all mu-, delta- and kappa-opioid receptor-mediated functions, whereas addition of the epsilon (epsilon)-opioid-receptor antagonist, beta-endorphin(1-27) prevents these effects of etorphine. Furthermore, after markedly enhancing excitatory opioid receptor functions in DRG neurons by treatment with GM1 ganglioside or pertussis toxin, etorphine shows excitatory agonist action on non-mu-/delta-/kappa-opioid receptor functions in these sensory neurons, in contrast to its usual potent antagonist action on mu-, delta- and kappa-excitatory receptor functions in naive and even in chronic morphine-treated cells which become supersensitive to the excitatory effects of mu-, delta- and kappa-opioid agonists. This weak excitatory agonist action of etorphine on non-mu-/delta-/kappa-opioid receptor functions may account for the tolerance and dependence observed after chronic treatment with extremely high doses of etorphine in vivo.
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PMID:Etorphine elicits anomalous excitatory opioid effects on sensory neurons treated with GM1 ganglioside or pertussis toxin in contrast to its potent inhibitory effects on naive or chronic morphine-treated cells. 900 33

alpha-Melanocyte-stimulating hormone (alpha-MSH, alpha-melanotropin) and agouti control the switch between eumelanin and pheomelanin synthesis in mammalian melanocytes. Here we investigated interactions between alpha-MSH, agouti protein, cAMP elevating agents and phorbol ester on mouse B16 melanoma cells. Agouti (Kd 3.7 nmol/l) and alpha-MSH (Kd 2.3 nmol/l) had similar affinities to the MC1 melanocortin receptor. Both alpha-MSH and agouti induced MC1 receptor down-regulation. Agouti antagonized melanogenesis induced by alpha-MSH, forskolin, cholera toxin (CT), and pertussis toxin (PT). It also reduced the constitutive melanin formation of long-term cultures. Cell proliferation was inhibited by agouti (43% at 100 nM). This effect was reversed by alpha-MSH, forskolin, or CT. B16-G4F cells, a cell variant that lacks the MC1 receptor, did not respond to agouti. From these results we conclude that agouti shows the characteristics of an inverse agonist acting through the MC1 receptor.
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PMID:Interactions of alpha-melanotropin and agouti on B16 melanoma cells: evidence for inverse agonism of agouti. 902 82

A nonisotopic, immunoelectrophoretic technique was used to analyze the characteristics of opioid-evoked activation of Gi2/ G(x/z) transducer proteins of mouse periaqueductal gray matter membranes. In the presence of picomolar concentrations of guanosine 5'-O-(3-thiotriphosphate), the opioid agonists promoted concentration-dependent increases of immunoreactivity associated with free Gi2alpha and G(x/z)alpha subunits. [D-Ala2,N-MePhe4, Gly-ol5]enkephalin and morphine (preferential agonists at mu opioid receptors) and beta-endorphin-(1-31) (an agonist at mu/delta opioid receptors) activated G(x/z) proteins. In contrast, the agonists of delta opioid receptors, [D-Ala2]deltorphin II and [D-Pen(2,5)]enkephalin, displayed little or no activity on this pertussis toxin resistant regulatory protein. Although exhibiting diverse efficacy, all the opioids studied activated Gi2 transducer proteins. [D-Ala2,N-MePhe4,Gly-ol5]enkephalin and [D-Ala2]-deltorphin II were more potent at Gi2alpha subunits than at G(x/z)alpha subunits. The opioid antagonist naloxone displayed a competitive profile in reducing the activation of G proteins promoted by morphine. Moreover, [D-Pen(2,5)]enkephalin antagonized the releasing effect exerted by [D-Ala2]deltorphin II on Gi2alpha and G(x/z)alpha subunits. N,N-diallyl-Tyr-Aib-Aib-Phe-Leu (ICI-174864) reduced the G alpha-related immunosignals promoted by agonists of delta opioid receptors. Therefore, it is suggested that opioids exhibit marked differences in efficacy and/or potency in the activation of Gi2 and G(x/z) transducer proteins in mouse periaqueductal gray matter.
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PMID:Opioids binding mu and delta receptors exhibit diverse efficacy in the activation of Gi2 and G(x/z) transducer proteins in mouse periaqueductal gray matter. 910 43

We investigated non-genomic mechanisms of glucocorticoid negative feedback regulation on pituitary corticotroph cells using the AtT20 mouse corticotroph tumor cell line. A synthetic glucocorticoid dexamethasone (100 nM) potently suppressed forskolin-induced cAMP generation, adrenocorticotropin (ACTH) secretion, and proopiomelanocortin gene expression. When de novo gene expression was inhibited by actinomycin D (1 microM), dexamethasone still suppressed cAMP efflux and ACTH release, although less potently. Interestingly, under the same conditions, pretreatment of the cells with pertussis toxin (50 ng/ml) completely abolished the suppressive effect of dexamethasone on both parameters. These results suggest that non-genomic and genomic mechanisms are involved in the glucocorticoid negative regulation of ACTH expression, and a pertussis toxin-sensitive GTP-binding protein might, at least partly, participate in the non-genomic effect.
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PMID:Non-genomic mechanisms of glucocorticoid inhibition of adrenocorticotropin secretion: possible involvement of GTP-binding protein. 919 85


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