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)

A model employing perfusion of artificial cerebrospinal fluid from the lateral ventricle to the cisterna magna in the halothane anesthetized rat was used to study beta-endorphin release in the brain. Injection of 75 micrograms capsaicin into the lumbar intrathecal space released beta-endorphin immunoreactivity into perfusate. The release was blocked by intrathecal pretreatment with 1.25 mg lidocaine and the capsaicin receptor antagonist capsazepine (92 micrograms), showing that the release is caused by binding of capsaicin to a spinal receptor. The release was also blocked by intrathecal pretreatment with the NMDA antagonist MK-801 (3 micrograms) and the NK-1 receptor antagonist CP96,345 (200 micrograms), whereas the AMPA receptor antagonist NBQX (6 micrograms) yielded no significant inhibition. Surprisingly, morphine (30 micrograms) and sufentanil (1.5 micrograms) did not prevent release of beta-endorphin immunoreactivity, although blocking the cardiovascular responses to a noxious heat stimulus. High performance liquid chromatography characterization of perfusates collected after capsaicin injection showed that all beta-endorphin immunoreactivity coeluted with authentic beta-endorphin1-31. beta-Endorphin immunoreactivity in plasma was increased 10 min, but not 25 min, after capsaicin injection. Capsaicin injection abolished the motor and cardiovascular responses to tail immersion in 52.5 degrees C water. Addition of MK-801 (10(-4) mol/l) to the lateral ventricle-cisterna magna perfusate blocked the capsaicin-induced beta-endorphin release, showing that our previous demonstration of an NMDA receptor regulating arcuate nucleus beta-endorphin neuron activity has functional significance. We conclude that in this in vivo, anesthetized preparation including three hot water tail immersions, beta-endorphin can be released into a ventriculo-cisternal perfusate, by activation of the central axons of small primary afferent neurons by capsaicin. These data support the idea that central beta-endorphin may be released in response to prolonged, intense noxious stimulation.
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PMID:Release of beta-endorphin immunoreactivity into ventriculo-cisternal perfusate by lumbar intrathecal capsaicin in the rat. 892 84

Cannabinoid receptor 2 (CB2) agonists provide the potential for treating chronic pain states without CNS effects associated with CB1 receptor activation. Animal models suggest that they act mainly via non-neuronal cells, possibly inhibition of inflammatory cells in the periphery or CNS, or via release of beta-endorphin; however, the clinical relevance and mechanism of analgesic action is uncertain. Here, we demonstrate colocalisation of CB2 with CB1 and the capsaicin receptor TRPV1 in human dorsal root ganglion (DRG) sensory neurons and increased levels of CB2 receptors in human peripheral nerves after injury, particularly painful neuromas. In primary cultures of human DRG neurons, selective CB2 agonists blocked activation of inward cation currents and elevation of cytoplasmic Ca2+ in response to capsaicin. These inhibitory effects were reversed by GW818646X a CB2 antagonist, and 8-bromo cAMP, but not by SR141716 a CB1 antagonist, or naloxone. Thus CB2 receptor agonists functionally inhibited nociceptive signalling in human primary sensory neurons via a mechanism shared with opioids, of adenylyl cyclase inhibition, but not via mu-opioid receptors. We conclude that CB2 agonists deserve imminent clinical trials for nociceptive, inflammatory and neuropathic chronic pain, in which capsaicin or heat-activated responses via TRPV1 may provide a clinical marker.
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PMID:Cannabinoid receptor CB2 localisation and agonist-mediated inhibition of capsaicin responses in human sensory neurons. 1869 62

When core body temperature increases, appetite and food consumption decline. A higher core body temperature can occur during exercise, during exposure to warm environmental temperatures, or during a fever, yet the mechanisms that link relatively warm temperatures to appetite suppression are unknown. A recent study in PLOS Biology demonstrates that neurons in the mouse hypothalamus that express pro-opiomelanocortin (POMC), a neural population well known to suppress food intake, also express a temperature-sensitive ion channel, transient receptor potential vanilloid 1 (TRPV1). Slight increases in body temperature cause a TRPV1-dependent increase in activity in POMC neurons, which suppresses feeding in mice. Taken together, this study suggests a novel mechanism linking body temperature and food-seeking behavior.
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PMID:POMC neurons in heat: A link between warm temperatures and appetite suppression. 2973 35