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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review is concerned with recent literature on the neural control of the pituitary pars intermedia of the amphibian Xenopus laevis. This aquatic toad adapts skin colour to the light intensity of its environment, by releasing the proopiomelanocortin (POMC)-derived peptide alpha-MSH (alpha-melanophore-stimulating hormone) from melanotrope cells. The activity of these cells is controlled by brain centers of which the hypothalamic suprachiasmatic and magnocellular nuclei, respectively, inhibit and stimulate both biosynthesis and release of alpha-MSH. The suprachiasmatic nucleus secretes dopamine, GABA, and NPY from synaptic terminals on the melanotropes. The structure of the synapses depends on the adaptation state of the animal. The inhibitory transmitters act via cAMP. Under inhibition conditions, melanotropes actively export cAMP, which might have a first messenger action. The magnocellular nucleus produces CRH and TRH. CRH, acting via cAMP, and TRH stimulate POMC-biosynthesis and POMC-peptide release. ACh is produced by the melanotrope cell and acts in an autoexcitatory feedback on melanotrope M1 muscarinic receptors to activate secretory activity. POMC-peptide secretion is driven by oscillations of the [Ca2+]i, which are initiated by receptor-mediated stimulation of Ca2+ influx via N-type calcium channels. The hypothalamic neurotransmitters and ACh control Ca2+ oscillatory activity. The structural and functional aspects of the various neural and endocrine steps in the regulation of skin colour adaptation by Xenopus reveal a high degree of plasticity, enabling the animal to respond optimally to the external demands for physiological adaptation.
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PMID:Background adaptation by Xenopus laevis: a model for studying neuronal information processing in the pituitary pars intermedia. 940 33

We have tried to investigate the possible interaction between the gabaergic system and alpha-MSH at a cellular level in an in vitro model of male albino rats tissue slices containing accumbens and caudate-putamen nuclei. Alpha-MSH alone increases cAMP levels, as does diazepam and phaclofen; however, these effects were blocked by SCH-23390. Both flumazenil and baclofen induced a decrease in the cAMP content. When both alpha-MSH and gabaergic agents were incubated together, cAMP levels were modified. It can be assumed that cAMP production by the neuropeptide and the gabaergic agents could be linked to the activation of dopaminergic D1 receptors. The latter receptors had no prominent effect on the interaction between alpha-MSH and the GABA agonists and antagonists. In summary, our results suggested that alpha-MSH and GABA system could be biochemically linked to produce a cellular effect.
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PMID:Interaction between alpha-MSH and gabaergic agents upon striatal cAMP levels: an in vitro model. 949 72

Whole-cell patch-clamp and extracellular field recordings were obtained from 450-microns-thick brain slices of infant rats (10-13 days postnatal) to determine the actions of corticotropin-releasing hormone on glutamate- and GABA-mediated synaptic transmission in the hippocampus. Synthetic corticotropin-releasing hormone (0.15 microM) reversibly increased the excitability of hippocampal pyramidal cells, as determined by the increase in the amplitude of the CA1 population spikes evoked by stimulation of the Schaffer collateral pathway. This increase in population spike amplitude could be prevented by the corticotropin-releasing hormone receptor antagonist alpha-helical (9-41)-corticotropin-releasing hormone (10 microM). Whole-cell patch-clamp recordings revealed that, in the presence of blockers of fast excitatory and inhibitory synaptic transmission, corticotropin-releasing hormone caused only a small (1-2 mV) depolarization of the resting membrane potential in CA3 pyramidal cells, and it did not significantly alter the input resistance. However, corticotropin-releasing hormone, in addition to decreasing the slow afterhyperpolarization, caused an increase in the number of action potentials per burst evoked by depolarizing current pulses. Corticotropin-releasing hormone did not significantly change the frequency, amplitude or kinetics of miniature excitatory postsynaptic currents. However, it increased the frequency of the spontaneous excitatory postsynaptic currents in CA3 pyramidal cells, without altering their amplitude and single exponential rise and decay time constants. Corticotropin-releasing hormone did not change the amplitude of the pharmacologically isolated (i.e. recorded in the presence of GABAA receptor antagonist bicuculline) excitatory postsynaptic currents in CA3 and CA1 pyramidal cells evoked by stimulation of the mossy fibers and the Schaffer collaterals, respectively. Current-clamp recordings in bicuculline-containing medium showed that, in the presence of corticotropin-releasing hormone, mossy fiber stimulation leads to large, synchronized, polysynaptically-evoked bursts of action potentials in CA3 pyramidal cells. In addition, the peptide caused a small, reversible decrease in the amplitude of the pharmacologically isolated (i.e. recorded in the presence of glutamate receptor antagonists) evoked inhibitory postsynaptic currents in CA3 pyramidal cells, but it did not significantly alter the frequency, amplitude, rise and decay time constants of spontaneous or miniature inhibitory postsynaptic currents. These data demonstrate that corticotropin-releasing hormone, an endogenous neuropeptide whose intracerebroventricular infusion results in seizure activity in immature rats, has diverse effects in the hippocampus which may contribute to epileptogenesis. It is proposed that the net effect of corticotropin-releasing hormone is a preferential amplification of those incoming excitatory signals which are strong enough to reach firing threshold in at least a subpopulation of CA3 cells. These findings suggest that the actions of corticotropin-releasing hormone on neuronal excitability in the immature hippocampus may play a role in human developmental epilepsies.
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PMID:The pro-convulsant actions of corticotropin-releasing hormone in the hippocampus of infant rats. 952 63

Using whole-cell patch-clamp techniques, we show that oligosphere-derived oligodendrocyte progenitor cells (OP) display GABA-, glutamate-, 5-HT-, glycine- and acetylcholine-gated inward currents. When OP differentiate into oligodendrocytes (ODC), the amplitude of peak currents elicited by saturating concentrations of these transmitters decreases except for 5-HT. Intracellular Ca2+ concentration changes induced by microperfusion of glutamate, 5-HT, TRH, met-enkephalin and substance P were monitored using a fluo-3-based calcium imaging system. When OP cells differentiate into ODC, a global decrease of the proportion of responding cells is observed. During type-2 astrocytes commitment, this proportion decreases for 5-HT, TRH- and metenkephalin stimulations whereas it remains constant for substance P and glutamate. These data demonstrate a development regulation of neurotransmitter- and neuropeptide-induced responses within the oligodendroglial lineage.
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PMID:Developmental regulation of neuroligand-induced responses in cultured oligodendroglia. 960 52

The possible neurotransmitter role of corticotropin-releasing hormone (CRH) was studied in the primary somatosensory cortex of the rat. Electrical activity of single neurones was recorded in layers II-VI of cortex, and in the region of the locus coeruleus. Iontophoresis and pressure ejection were employed to locally apply CRH, and changes in spontaneous, synaptically driven and iontophoretically driven firing were examined. In the cortex, of 62 neurones recorded most (51) were completely unaffected by high and prolonged current/pressure ejections of CRH. Depression of firing was occasionally seen (8 of 62), while a very few (3) were weakly excited. Of 25 cells studied with vibrissal stimulation to evoke excitatory synaptic responses, responses in two cells were depressed and in two they were enhanced. Activity that was evoked by iontophoretic ejection of excitatory amino acids, such as glutamate, was depressed in 6 of 40 cells (none were enhanced). Such effects as were seen were weak and often difficult to reproduce. The effect of CRH on depressions produced by GABA was also tested in four experiments. No effects on the amplitude or duration of the depressions were observed. In contrast recordings made in the midbrain, in the region of the locus coeruleus, resulted in over half the neurones (11 of 20) showing clear reproducible excitatory responses to CRH applications. Solutions used in the experiments were analysed using chromatography, radioimmunoassay and bioassay, and no significant degradation of the peptide was found compared with the synthetic standard (CRH (1-41)). The data provide evidence against CRH acting as a neurotransmitter or modulator in primary cortex, suggesting that the CRH which is localized in certain types of cortical cells is involved in other processes.
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PMID:Electrophysiological evidence against a neurotransmitter role of corticotropin-releasing hormone (CRH) in primary somatosensory cortex. 963 May 25

To gain insight into the neurochemical pathologies contributing to AIDS dementia complex, neurotransmitter levels were measured in the brains of mice infected with the LP-BM5 leukemia retrovirus. These mice develop immunologic and cognitive deficits analogous to human HIV-1 infection. Met-enkephalin and substance-P levels declined approximately 50% in the striatum and hypothalamus beginning as early as 4 weeks after infection. Hippocampal met-enkephalin levels were reduced to 50% only at 12 weeks after inoculation. Significant decreases (60-70%) in acetylcholine concentrations were observed in the striatum, cerebral cortex and hippocampus by 12 weeks after virus inoculation, while striatal GABA concentrations decreased to 50-60% at 8-12 weeks after infection. Striatal somatostatin levels were unchanged. Administration of the NMDA receptor antagonists MK-801 or LY 274614 ameliorated the decline in striatal met-enkephalin levels observed in mice after 8 weeks of infection. This pattern of neurotransmitter depletion and the ability of NMDA receptor antagonists to attenuate the loss of striatal met-enkephalin are consistent with an excitotoxic lesion. Thus, the elevation of glutamate levels secondary to glial activation may contribute to the contemporaneous development of cognitive deficits observed in mice infected with the LP-BM5 virus.
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PMID:The pattern of neurotransmitter alterations in LP-BM5 infected mice is consistent with glutamatergic hyperactivation. 963 May 62

Enkephalins are known to have a profound effect on hippocampal inhibition, but the possible endogenous source of these neuropeptides, and their relationship to inhibitory interneurons is still to be identified. In the present study we analysed the morphological characteristics of met-enkephalin-immunoreactive cells in the CA1 region of the rat and guinea-pig hippocampus, their coexistence with other neuronal markers and their target selectivity at the light and electron microscopic levels. Several interneurons in all subfields of the hippocampus were found to be immunoreactive for met-enkephalin. In the guinea-pig, fibres arising from immunoreactive interneurons were seen to form a plexus in the stratum oriens/alveus border zone, and basket-like arrays of boutons on both enkephalin-immunoreactive and immunonegative cell bodies in all strata. Immunoreactive boutons always established symmetric synaptic contacts on somata and dendritic shafts. Enkephalin-immunoreactive cells co-localized GABA, vasoactive intestinal polypeptide and calretinin. Postembedding immunogold staining for GABA showed that all the analysed enkephalin-immunoreactive boutons contacted GABAergic postsynaptic structures. In double-immunostained sections, enkephalin-positive axons were seen to innervate calbindin D28k-, somatostatin-, calretinin- and vasoactive intestinal polypeptideimmunoreactive cells with multiple contacts. Based on these characteristics, enkephalin-containing cells in the hippocampus are classified as interneurons specialized to innervate other interneurons, and represent a subset of vasoactive intestinal polypeptide- and calretinin-containing cells. The striking match of ligand and receptor distribution in the case of enkephalin-mediated interneuronal communication suggests that this neuropeptide may play an important role in the synchronization and timing of inhibition involved in rhythmic network activities of the hippocampus.
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PMID:Enkephalin-containing interneurons are specialized to innervate other interneurons in the hippocampal CA1 region of the rat and guinea-pig. 975 Nov 50

1. The actions of opioid receptor agonists on the calcium channel currents (IBa) of acutely dissociated periaqueductal grey (PAG) neurons from C57B16/J mice and mutant mice lacking the first exon of the mu-opioid receptor (MOR-1) were examined using whole cell patch clamp techniques. These effects were compared with the GABA(B)-receptor agonist baclofen. 2. The endogenous opioid agonist methionine-enkephalin (met-enkephalin, pEC50 6.8, maximum inhibition 40%), the putative endogenous mu-opioid agonist endomorphin-1 (pEC50 6.2, maximum inhibition 35%) and the mu-opioid selective agonist DAMGO (Tyr-D-Ala-Gly-N-Me-Phe-Gly-ol enkephalin, pEC50 6.9, maximum inhibition 40%) inhibited IBa in 70% of mouse PAG neurons. The inhibition of IBa by each agonist was completely prevented by the mu-receptor antagonist CTAP (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2). The delta-opioid receptor agonists DPDPE ([D-Pen2,5]enkephalin, 1 microM) and deltorphin II (1 microM), and the kappa-opioid receptor agonist U-69593 (1-10 microM), did not affect IBa in any cell tested. 3. The GABA(B) agonist baclofen inhibited IBa in all neurons (pEC50 5.9, maximum inhibition 42%). 4. In neurons from the MOR-1 deficient mice, the mu-opioid agonists met-enkephalin, DAMGO and endomorphin-1 did not inhibit IBa, whilst baclofen inhibited IBa in a manner indistinguishable from wild type mice. 5. A maximally effective concentration of endomorphin-1 (30 microM) partially (19%), but significantly (P<0.005), occluded the inhibition of IBa normally elicited by a maximally effective concentration of met-enkephalin (10 microM). 6. This study indicates that mu-opioid receptors, but not delta- or kappa-opioid receptors, modulate somatic calcium channel currents in mouse PAG neurons. The putative endogenous mu-agonist, endomorphin-1, was a partial agonist in mouse PAG neurons.
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PMID:Mu-opioid receptor modulation of calcium channel current in periaqueductal grey neurons from C57B16/J mice and mutant mice lacking MOR-1. 1032 86

Intracranial self-administration (ICSA) and intracranial place conditioning (ICPC) methodologies have been mainly used to study drug reward mechanisms, but they have also been applied toward examining brain reward mechanisms. ICSA studies in rodents have established that the ventral tegmental area (VTA) is a site supporting morphine and ethanol reinforcement. ICPC studies confirmed that injection of morphine into the VTA produces conditioned place preference (CPP). Further confirmation that activation of opioid receptors within the VTA is reinforcing comes from the findings that the endogenous opioid peptide met-enkephalin injected into the VTA produces CPP, and that the mu- and delta-opioid agonists, DAMGO and DPDPE, are self-infused into the VTA. Activation of the VTA dopamine (DA) system may produce reinforcing effects in general because (a) neurotensin is self-administered into the VTA, and injection of neurotensin into the VTA produces CPP and enhances DA release in the nucleus accumbens (NAC), and (b) GABA(A) antagonists are self-administered into the anterior VTA and injections of GABA(A) antagonists into the anterior VTA enhance DA release in the NAC. The NAC also appears to have a major role in brain reward mechanisms, whereas most data from ICSA and ICPC studies do not support an involvement of the caudate-putamen in reinforcement processes. Rodents will self-infuse a variety of drugs of abuse (e.g. amphetamine, morphine, phencyclidine and cocaine) into the NAC, and this occurs primarily in the shell region. ICPC studies also indicate that injection of amphetamine into the shell portion of the NAC produces CPP. Activation of the DA system within the shell subregion of the NAC appears to play a key role in brain reward mechanisms. Rats will ICSA the DA uptake blocker, nomifensine, into the NAC shell; co-infusion with a D2 antagonist can block this behavior. In addition, rats will self-administer a mixture of a D1 plus a D2 agonist into the shell, but not the core, region of the NAC. The ICSA of this mixture can be blocked with the co-infusion of either a D1 or a D2 antagonist. However, the interactions of other transmitter systems within the NAC may also play key roles because NMDA antagonists and the muscarinic agonist carbachol are self-infused into the NAC. The medial prefrontal (MPF) cortex supports the ICSA of cocaine and phencyclidine. The DA system also seems to play a role in this behavior since cocaine self-infusion into the MPF cortex can be blocked by co-infusing a D2 antagonist, or with 6-OHDA lesions of the MPF cortex. Limited studies have been conducted on other CNS regions to elucidate their role in brain and drug reward mechanisms using ICSA or ICPC procedures. Among these regions, ICPC findings suggest that cocaine and amphetamine are rewarding in the rostral ventral pallidum (VP); ICSA and ICPC studies indicate that morphine is rewarding in the dorsal hippocampus, central gray and lateral hypothalamus. Finally, substance P mediated systems within the caudal VP (nucleus basalis magnocellularis) and serotonin systems of the dorsal and median raphe nuclei may also be important anatomical components involved in brain reward mechanisms. Overall, the ICSA and ICPC studies indicate that there are a number of receptors, neuronal pathways, and discrete CNS sites involved in brain reward mechanisms.
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PMID:Localization of brain reinforcement mechanisms: intracranial self-administration and intracranial place-conditioning studies. 1037 70

The lateral division of the central nucleus of the amygdala (CEAl) and the oval nucleus of the bed nucleus of the stria terminalis (BSTov) have been linked closely anatomically and functionally. To determine whether these regions may be subdivided further on a neurochemical basis, dual in situ hybridization was used to determine the colocalization of corticotropin-releasing hormone (CRH), enkephalin (ENK), or neurotensin (NT) with glutamic acid decarboxylase isoforms 65 and 67 [used concurrently as a marker for gamma-aminobutyric acid GABA] in these nuclei. It was found that, for both regions, each peptide invariably was localized in a GABAergic cell. Although there was a similar overlap in the distribution of NT with ENK in the BSTov and CEAl, it was observed that CRH and ENK rarely were colocalized in either nucleus. To determine whether these distinct neuronal populations could be activated differentially, male rats were given a systemic injection of interleukin-1beta (IL-1beta; 5 microg/kg, i.p.), a stimulus that results in a robust increase in c-fos mRNA expression in the BSTov and CEAl. The neurochemical identity of these activated neurons showed striking similarities between the BSTov and the CEAl; All IL-1beta-responsive cells were GABAergic, the majority of c-fos- positive cells expressed ENK mRNA (BSTov, 81%; CEAl, 94%), and some expressed NT mRNA (BSTov, 23%; CEAl, 22%), whereas very few expressed CRH mRNA (BSTov, 4%; CEAl, 1%). These data provide evidence for the existence of discrete neural circuits within the BSTov and CEAl, and the similarities in the patterns of neurochemical colocalization in these nuclei are consistent with the concept of an extended amygdala. Furthermore, these data indicate that intraperitoneal IL-1beta recruits neurochemically distinct pathways within the BSTov and CEAl, and it is suggested that this differential activation may mediate specific aspects of immune, limbic, and/or autonomic processes.
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PMID:Distinct neurochemical populations in the rat central nucleus of the amygdala and bed nucleus of the stria terminalis: evidence for their selective activation by interleukin-1beta. 1046 74


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