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)

Our previous studies have demonstrated that supraspinal GABAergic receptors are differentially involved in the antinociception induced by morphine and beta-endorphin given intracerebroventricularly (i.c.v.) in the tail-flick and hot-plate tests. These two models employed a phasic, thermal nociceptive stimulus. The present study was designed to examine the possible involvement of supraspinal GABAergic receptors in opioid-induced antinociception in the formalin test. Morphine (1 microg) and beta-endorphin (1 microg) given i.c.v. displayed the almost complete inhibitory effects against the hyperalgesic response in both phases. Muscimol (75-100 ng) and baclofen (5-10 ng) injected i.c.v. produced the hypoalgesic response in the both phases. The hypoalgesic response induced by muscimol and baclofen observed during the second phase was more pronounced than that observed during the second phase. Baclofen (2.5 ng), at the dose which did not affect the hyperalgesic response, resulted in a significant reversal of the i.c.v. administered beta-endorphin-induced hypoalgesic response observed during the second, but not the first, phase. However, the hypoalgesic response induced by i.c.v. administered morphine was not changed by the same dose of muscimol or baclofen injected i.c.v. Our results indicate that, at the supraspinal level, GABA(B)receptors appear to be involved in the modulation of antinociception induced by supraspinally administered beta-endorphin, but not morphine, in the formalin test model.
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PMID:Differential modulation by baclofen on antinociception induced by morphine and beta-endorphin administered intracerebroventricularly in the formalin test. 1065 37

The effect of muscimol or baclofen injected intrathecally (i.t.) on the inhibition of the tail-flick response induced by morphine and beta-endorphin administered i.t. was studied in ICR mice. The i.t. injection of muscimol (100 ng) or baclofen (10 ng) alone did not affect the basal inhibition of the tail-flick response. Morphine (0.2 microg) and beta-endorphin (0.1 microg) caused only slight inhibition of the tail-flick response. Baclofen, but not muscimol, injected i.t. enhanced the inhibition of the tail-flick response induced by i.t. administered morphine. Both muscimol and baclofen injected i.t. significantly enhanced i.t. injected beta-endorphin-induced inhibition of the tail-flick response. Our results suggest that the GABA(B), but not GABA(A), receptors located in the spinal cord appear to be involved in enhancing the inhibition of the tail-flick response induced by morphine administered spinally. In addition, both GABA(A) and GABA(B) receptors are involved in enhancing the inhibition of the tail-flick response induced by beta-endorphin administered i.t.
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PMID:Differential potentiative effects of GABA receptor agonists in the production of antinociception induced by morphine and beta-endorphin administered intrathecally in the mouse. 1066 91

The effect of GABA receptors agonists on the stress-induced beta-endorphin levels in the preoptic area and mediobasal hypothalamus of the intact and prenatally stressed male albino rats was studied. It has been found out that stimulation of GABAa-receptor complex by means of the muscimol leads to increasing of beta-endorphin levels in the preoptic area and mediobasal hypothalamus of the control animals. GABAb receptor activation by means of the baclofen decreases opioids level in the mediobasal hypothalamus. Prenatal stress eliminates stimulant effect of the muscimol on beta-endorphin levels in the investigated brain structures and leads to the opioid level decreasing after baclofen influence in preoptic area.
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PMID:[The mechanisms of the GABA-ergic regulation of beta-endorphin levels in the hypothalamic structures of prenatally stressed male rats]. 1086 69

A single dose of nicotine given to mice induces first a rapid decrease (presumed release/enhanced degradation) and then a rise (presumed synthesis/enhanced accumulation) of met-enkephalin (Met-Enk) in dorsal and ventral striatum observed at 30 and 60 min post-treatment, respectively. These studies investigated whether the nicotine effect on Met-Enk was mediated indirectly, in part, via other neurotransmitters known to be released by nicotine. Based on the ability of selective antagonists of dopamine (Sch 23390, D1; Sulpiride, D2), glutamate (CPP, competitive NMDA; dizocilpine, non-competitive NMDA; NBQX, AMPA) and GABA (bicuculline, GABA(A); Sch 50911, GABA(B)) receptors, to inhibit or enhance the response to nicotine, we conclude that nicotine alters striatal Met-Enk, in part, via glutamate NMDA and AMPA receptors. These findings further support the notion that glutamate might play a role in the pharmacology of nicotine.
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PMID:Glutamate receptors participate in the nicotine-induced changes of met-enkephalin in striatum. 1099 37

The endogenous opioid neurotransmitter beta-endorphin (beta-END), a product of the proopiomelanocortin (POMC) gene, is strongly implicated in the control of the female reproductive cycle, stress responses, and antinociception. Using selective gene targeting, we have generated a strain of mice that do not express any beta-END. These mice exhibit both normal reproduction and normal basal and stress-induced hypothalamic-pituitary-axis activity, but exhibit a significantly attenuated opioid-mediated stress-induced analgesia. To further understand the cellular bases of these responses, we have studied mediobasal hypothalamic (MBH) neurons, including POMC neurons, using whole-cell patch recording in an in vitro slice preparation. Twenty-seven MBH cells were recorded in wild-type and 25 MBH cells were recorded in beta-END knockout mice. Neurons from both genotypes showed a significant positive correlation between DAMGO concentration (from 30 nM to 10 microM) and the induced outward K(+) current. The genotypes did not differ, however, in either the DAMGO-induced maximum outward current response or EC(50), or for the maximal response to the GABA(B) agonist baclofen. Furthermore, quantitative receptor autoradiography utilizing (3)H-DAMGO did not reveal any differences in total mu-opioid receptor binding between genotypes. Therefore, we conclude that the complete absence of beta-END throughout development did not alter either the expression of mu-opioid receptors or their coupling to K(+) channels in MBH neurons.
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PMID:Effect of the mu-opioid agonist DAMGO on medial basal hypothalamic neurons in beta-endorphin knockout mice. 1107 Apr 24

Corticotropin releasing factor is a 41 amino acid peptide that is present in afferent systems that project to the cerebellum. In the adult, this peptide modulates the activity of Purkinje cells by enhancing their responsiveness to excitatory amino acids. Two different types of corticotropin releasing factor receptors, designated type 1 and type 2, have been identified. The purpose of this study is to use immunohistochemistry to identify which corticotropin releasing factor receptors are present in the cerebellum of the adult mouse and to determine their cellular distribution. Receptor type 1 immunostaining is present throughout all lobules of the cerebellar cortex. Distinct labeling is present over the somas of most, if not all, Purkinje cells as well as the primary dendrites of Purkinje cells located at the base of vermal folia. In vermal lobules V, VI, VIII and IX numerous glial fibrillary acidic protein immunoreactive processes, oriented radially in the molecular layer, also are immunoreactive for receptor type 1. In the granule cell layer, scattered type 1 immunoreactive puncta are present throughout most cerebellar lobules. Receptor type 2 immunoreactive puncta are present throughout the molecular layer in all lobules. In addition, scattered basket and/or stellate cells, identified with a GABA antibody, are immunopositive for the type 2 receptor. In the Purkinje cell layer, the type 2 receptor immunolabeling is confined to the basal pole of the Purkinje cell including the initial axonal segment. In the granule cell layer, labeling is present over large cell bodies, and their initial axonal segments. These are likely to be Golgi cells, based on their co-staining with GABA. Finally, numerous elongated processes within the white matter, which are likely to be axons, also are type 2 immunoreactive. These data indicate that both types of corticotropin releasing factor receptor are present in the mouse cerebellum. However, the unique distribution of the two types of receptor strongly suggests a differential role for corticotropin releasing factor in modulating the activity of neurons, axons and glial cells via cell-specific ligand-receptor interactions.
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PMID:Cellular localization of corticotropin releasing factor receptors in the adult mouse cerebellum. 1111 57

Cultures of embryonic day 17 (E17) rat adrenal and neonatal bovine adrenal cells were conditionally immortalized with the temperature-sensitive allele of SV40 large T antigen (tsTag) and chromaffin cell lines established. Indicative of the adrenal chromaffin phenotype, these cells expressed immunoreactivity (ir) for tyrosine hydroxylase (TH), the first enzyme in the synthetic pathway for catecholamines. At permissive temperature in vitro (33 degrees C), these chromaffin cells are proliferative, have a typical rounded chromaffin-like morphology, and contain detectable TH-ir. At nonpermissive temperature in vitro (39 degrees C), these cells stop proliferating and express increased TH-ir. When these immortalized chromaffin cells were transplanted in the lumbar subarachnoid space of the spinal cord I week after a unilateral chronic constriction injury (CCI) of the rat sciatic nerve, they survived longer than 7 weeks on the pia mater around the spinal cord and continued to express TH-ir. Conversely, grafted chromaffin cells lost Tag-ir after transplant and Tag-ir was undetectible in the grafts after 7 weeks in the subarachnoid space. At no time did the grafts form tumors after transplant into the host animals. These grafted chromaffin cells also expressed immunoreactivities for the other catecholamine-synthesizing enzymes 7 weeks after grafting, including: dopamine-beta-hydroxylase (DbetaH) and phenylethanolamine-N-methyltransferase (PNMT). The grafted cells also expressed detectable immunoreactivities for the opioid met-enkephalin (ENK), the peptide galanin (GAL), and the neurotransmitters y-aminobutyric acid (GABA) and serotonin (5-HT). Furthermore, after transplantation, tactile and cold allodynia and tactile and thermal hyperalgesia induced by CCI were significantly reduced during a 2-8-week period, related to the chromaffin cell transplants. The maximal antinociceptive effect occurred 1-3 weeks after grafting. Control adrenal fibroblasts, similarly immortalized and similarly transplanted after CCI, did not express any of the chromaffin antigenic markers, and fibroblast grafts had no effect on the allodynia and hyperalgesia induced by CCI. These data suggest that embryonic and neonatal chromaffin cells can be conditionally immortalized and will continue to express the phenotype of primary chromaffin cells in vitro and in vivo; grafted cells will ameliorate neuropathic pain after nerve injury and can be used as a homogeneous source to examine the mechanisms by which chromaffin transplants reverse chronic pain. The use of such chromaffin cell lines that are able to deliver antinociceptive molecules in models of chronic pain after nerve and spinal cord injury (SCI) offers a novel approach to pain management.
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PMID:Initial characterization of the transplant of immortalized chromaffin cells for the attenuation of chronic neuropathic pain. 1114 61

Using the latency for tail-flick after thermal stimulation we have assessed the effects of alpha-, gamma(1)- and gamma(2)-MSH on nociceptive threshold in the mice. Intracisternal injections of gamma(2)-MSH induced a distinct analgesia, while gamma(1)-MSH in the same doses gave only a minor analgesia. Intracisternal alpha-MSH instead gave a short-term hyperalgesia. The effect of gamma(2)-MSH was not blocked by any of the MC(4)/MC(3)receptor antagonist HS014, naloxone or by the prior intracisternal administrations of gamma(1)-MSH. However, the gamma(2)-MSH analgesic response was completely attenuated by treating animals with the GABA(A)antagonist bicuculline. The gamma(2)-MSH analgesic effect was moreover additive to the analgesia afforded by muscimol and ethanol, but not to that afforded by diazepam. In addition both gamma(1)- and gamma(2)-MSH induced moderate catalepsy, but could at the same time attenuate haloperidol induced catalepsia. We conclude that gamma(2)-MSH mediates a central analgesic effect via GABA-receptor dependent pathway that is distinct from melanocortic- and opioid-receptors. Moreover, the mechanism for gamma(2)-MSH's analgesic effect appears to be distinct from that causing moderate catalepsia by gamma-MSH's.
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PMID:The gamma(2)-MSH peptide mediates a central analgesic effect via a GABA-ergic mechanism that is independent from activation of melanocortin receptors. 1134 10

A number of studies have shown that activation of gamma-aminobutyric acid(B) (GABA(B)) receptors potentiates neurotransmitter-induced accumulation of cyclic AMP in brain slices, but the mechanisms involved in the facilitatory effect have not been fully elucidated. In the present study, we showed that in membranes of rat frontal cortex the GABA(B) receptor agonist (-)baclofen increased basal adenylyl cyclase activity and potentiated the maximal enzyme stimulation elicited by corticotropin-releasing hormone (CRH). The less active enantiomer (+)baclofen had no effect on cyclic AMP formation, whereas the natural agonist GABA mimicked the stimulatory action of (-)baclofen. In radioligand-binding experiments, the affinity and maximal binding capacity of (125)I-Tyr-CRH was not affected by (-)baclofen. The GABA(B) receptor antagonist CGP 55845A competitively counteracted the (-)baclofen potentiation of CRH-stimulated adenylyl cyclase activity with a pA(2) value of 6.70. Moreover, both (-)baclofen and GABA, but not (+)baclofen, caused a concentration-dependent stimulation of [(35)S]GTP gamma S binding to membrane G-proteins. The intracerebral injection of pertussis toxin significantly reduced the facilitatory effects of (-)baclofen on both basal and CRH-stimulated adenylyl cyclase activities. Moreover, membrane incubation with the GDP-bound form of the alpha subunit of transducin, a scavenger of G protein beta gamma subunits, blocked the stimulatory effects of (-)baclofen. The data indicate that in rat frontal cortex activation of GABA(B) receptors potentiates the CRH stimulation of adenylyl cyclase activity through a mechanism involving the beta gamma subunits of the pertussis toxin-sensitive G protein G(i)/G(o).
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PMID:Beta gamma-mediated enhancement of corticotropin-releasing hormone-stimulated adenylyl cyclase activity by activation of gamma-aminobutyric acid(B) receptors in membranes of rat frontal cortex. 1138 76

1. Whole-cell patch clamp recordings were made from rat rostral ventromedial medulla (RVM) neurons in vitro to investigate the cellular actions of the opioid-like receptor ORL1 (NOP), ligand nociceptin/orphanin FQ and other putative prepronociceptin products. 2. Primary and secondary RVM neurons were identified as responding to the kappa-opioid receptor agonist U-69593 (300 nM to 1 microM) and the mu- and delta-opioid receptor agonist met-enkephalin (10 microM), respectively. Both primary and secondary RVM neurons responded to nociceptin (3 nM to 1 microM) with an outward current that reversed polarity at -115 mV in brain slices and with inhibition of Ca(2+) channel currents in acutely isolated cells. 3. The putative ORL1 antagonist J-113397 (1 microM) produced no change in membrane current and abolished the outward current produced by nociceptin (100 nM). In contrast, Phe(1)psi(CH(2)-NH)Gly(2)]-nociceptin-(1-13)NH(2) (300 nM to 1 microM) alone produced an outward current and partially reduced the outward current produced by nociceptin (300 nM) when co-applied. 4. In brain slices nociceptin (300 nM) reduced the amplitude of evoked GABA(A) receptor-mediated inhibitory postsynaptic currents (IPSCs) but not non-NMDA receptor-mediated excitatory postsynaptic currents (EPSCs). 5. Met-enkephalin (10 microM), but not nociceptin (300 nM), reduced the rate of spontaneous miniature IPSCs in normal external potassium solution (K(+) 2.5 mM). In high external potassium (K(+) 17.5 mM), nociceptin reduced the rate of miniature IPSCs in the presence (Ca(2+) 2.4 mM, Mg(2+) 1.2 mM) but not in the absence of external calcium (Ca(2+) 0 mM, Mg(2+) 10 mM, Cd(2+) 10 microM). Nociceptin and met-enkephalin had no effect on the amplitude of miniature IPSCs. 6. The putative nociceptin precursor products nocistatin (rat prepronociceptin(125-132)) and rat prepronociceptin(154-181) had no effect on membrane currents, evoked IPSCs and evoked EPSCs. 7. These results indicate that nociceptin acts via the ORL1 receptor to directly inhibit both primary and secondary RVM neurons by activating a potassium conductance and by inhibiting calcium conductances. In addition, nociceptin inhibits GABA release within the RVM via a presynaptic Ca(2+)-dependent mechanism. Thus, nociceptin has the potential to exert both disinhibitory and inhibitory effects on neuronal action potential firing within the RVM.
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PMID:Actions of nociceptin/orphanin FQ and other prepronociceptin products on rat rostral ventromedial medulla neurons in vitro. 1148 14


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