Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Characterization of the distribution of the peptide-degrading enzyme neutral endopeptidase-24.11 (E.C. 3.4.24.11; NEP; enkephalinase) in the rat brainstem was examined by means of a unique fluorescent histochemical method. Enzyme staining was completely blocked by three potent NEP inhibitors (thiorphan, phosphoramidon, and JHF-26) at a concentration of 50 nM, supporting the specificity of this method to visualize sites of NEP activity selectively. At all levels of the brainstem, NEP was localized to cell bodies, cell processes or terminal-like fields and was localized to more than 90 distinct nuclei or subnuclei. In the mesencephalon these included the central gray, cuneiform n., dorsal and lateral tegmental n., inferior colliculus, interpeduncular n., lateral and medial geniculate n., central linear raphe n., mesencephalic n. of the trigeminal nerve, mammillary nuclei, occulomotor n., red n., superior colliculus, ventral n. of the lateral lemniscus, substantia nigra-ventral tegmental area, and the zona incerta. In the pons, NEP staining was restricted to fewer regions or nuclei, including the dorsal and ventral cochlear n., facial n., motor trigeminal n., principal sensory trigeminal n., parabrachial nuclei, pontine n., the oral and caudal pontine reticular n., pontine olivary nuclei, several pontine tegmental nuclei, pontine raphe nuclei, and the trapezoid n. In the cerebellum, staining was localized largely to the granule cell layer of the cerebellar cortex. Scattered staining was observed in the molecular cell layer. The medulla contained extensive NEP staining localized to nuclei that included the ambiguous n., dorsal motor n. of the vagus, hypoglossal n., inferior olivary n., prepositus hypoglossus n., solitary tract n., nuclei of the spinal tract of the trigeminal n., and the lateral, medial, and superior vestibular nuclei. Nuclei of the medullary reticular formation that were also richly stained for NEP included the raphe magnus n., raphe obscurus n., raphe pallidus n., dorsal, lateral, and ventral reticular nuclei of the medulla, and the gigantocellular, lateral paragigantocellular, linear, paramedian and parvicellular reticular nuclei. The widespread distribution of NEP in the brainstem suggests the existence of a number of functional systems, including the pathways involved in the mechanisms of pain and analgesia, which are potential targets of NEP inhibitors. In most regions, the distribution of NEP closely overlapped with that reported for the enkephalins, and showed a more restricted overlap with the reported distribution of substance P.
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PMID:Fluorescent histochemical localization of neutral endopeptidase-24.11 (enkephalinase) in the rat brainstem. 169 88

The NOP system is considered to be part of the opioid system, although it exerts antiopioid actions depending on the anatomical region where it is localized. This apparent controversy has lead to the hypothesis that the NOP system interacts with the classical opioid systems (mu, delta, kappa) and regulates/modulates their activity in relation to analgesia and the development of addiction to drugs. In order to shed light into the importance of the NOP system, we have analyzed the expression of NOP during zebrafish development, and the effect of its endogenous agonist nociceptin and the opioid agonist morphine on NOP expression. Our qPCR study show that the number of NOP transcripts is different at each developmental stage studied (0.5 hpf, 2.75 hpf, 3 hpf, 8 hpf, 16 hpf, 19 hpf, 22 hpf, 24 hpf, 30 hpf, 48 hpf, 60 hpf and 72 hpf). Nociceptin enhances NOP expression at 24 hpf but decreases the number of NOP copies at 48 hpf, whereas NOP expression decreases after morphine exposure at 24 hpf and 48 hpf. Also, our ISH analysis demonstrates that nociceptin causes a change in the distribution of NOP towards rostral areas at both developmental stages. Morphine produces similar changes to those of nociceptin although only at 48 hpf. The present work leads to the conclusion that the NOP system is important during embryogenesis. Exposure to drugs changes the expression level and localization of NOP, suggesting that also during development, NOP plays a role in the apparition of dependence and addiction to drugs.
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PMID:Expression of the nociceptin receptor during zebrafish development: influence of morphine and nociceptin. 1946 Jun 25