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)

A tabular synopsis is presented for articles concerned with the effects of peptides on the central nervous system that appeared in the journal Peptides from 1980-1985. A table arranged alphabetically by peptide and one arranged by effects, both listing routes of injection, species, direction of change, and qualifying notes, provides easy cross-referencing of peptides and their effects. Over 80 peptides and over 135 effects are listed. The list of peptides includes, but is not limited to: ACTH, angiotensin, bombesin, bradykinin, calcitonin, casomorphin, CCK, ceruletide, CGRP, CRF, dermorphin, DSIP, dynorphin, endorphins, enkephalins, GRF, gastrin, LHRH, litorin, metkephamid, MIF-l, motilin, MSH, NPY, NT, oxytocin, ranatensin, sauvagine, substances P and K, somatostatin, TRH, VIP, vasopressin, and vasotocin. The list of effects includes, but is not limited to: aggression, alcohol, analgesia, attention, avoidance, behavior, cardiovascular regulation, catalepsy, conditioned behavior, convulsions, dopamine binding and metabolism, discrimination, drinking, EEG, exploration, feeding, fever, gastric secretion, GI motility, grooming, learning, locomotor behavior, mating, memory, neuronal activity, open field, operant behavior, rearing, respiration, satiety, scratching, seizure, sleep, stereotypy, temperature, thermoregulation and tolerance.
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PMID:Central nervous system effects of peptides, 1980-1985: a cross-listing of peptides and their central actions from the first six years of the journal Peptides. 353 8

The knowledge of the amino acid sequence of both beta-lipotropin (beta-LPH) and gamma-LPH was the starting point that led to the hypothesis, considered revolutionary in 1967, that hormonal precursors exist. This concept was simultaneously proposed for proinsulin and applied later to other polypeptide hormones. The discovery of endorphins brought together two fields of research that were not related: the opiates and the so-called pituitary lipotropic hormones. The demonstration of specific brain opiate receptors led to the hypothesis of the existence of endogenous opiate ligands which could act as neurotransmittors. The isolation of such substances in the brain, first named enkephalins, revealed through their amino acid sequence their structural homology with the pituitary lipolytic hormones. The finding of a more potent opioid substance in the pituitary (beta-endorphin) that comprises the last 31 amino acids of beta-LPH shed a new light on the hypothesis proposed earlier which gave to beta-LPH a role as a precursor molecule. Finally, the addition of ACTH completed a putative multipotent precursor model that has been recently named pro-opiomelanocortin. Pulse-chase experiments have definitely proven that beta-endorphin is a maturation product of a large precursor also containing ACTH and MSH. In other studies, many groups have suggested that endorphins play important roles as possible neuromodulators in pain transmission, in analgesia, in tolerance and dependence, as well as on behavior and endocrine regulations, mainly those related to the hypothalamo-pituitary axes. The elucidation of the biosynthetic process or processes of cerebral endorphins (either enkephalins or beta-endorphin) is of primary importance in order ot understand better their biological as well as regulatory functions. These studies should also be applicable to the biosynthesis of all the other neuronal peptide hormones. It is hoped that they will provide new tools for the study of some important central nervous system functions, such as pain and endocrine control and the physiopathology of behavioral diseases.
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PMID:[Endorphins: structure, roles and biogenesis]. 626 34

In a completely crossed, double blind designed study, six rats received intraventricular injections of 0.1, 1.0 and 10 micrograms of alpha-MSH and a placebo. The rats were tested for response to painful thermal stimuli with the tail-flick test. All of the doses of alpha-MSH produced hyperalgesia during the first 20 min of testing. Only the 1.0 microgram dose of alpha-MSH produced hyperalgesia throughout the 80 min course of the experiment. This study, coupled with previous reports that MSH/ACTH fragments may attenuate morphine-induced analgesia, suggest that MSH can have opposite actions from those of the endorphins. It is possible that alpha-MSH and related peptides may be endogenous anti-opiates.
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PMID:Intraventricular administration of MSH induces hyperalgesia in rats. 729 Oct 44

The peptide products of the pro-opiomelanocortin (POMC) gene have established roles in the control of physiological processes as diverse as adrenal steroidogenesis, skin pigmentation, analgesia and inflammation. In the last 5 years, evidence accumulated from murine and human genetic models of disrupted melanocortin signalling has firmly established a central role for a population of hypothalamic neurons expressing POMC in the control of appetite and body weight. Of the five known melanocortin receptors, the MC4R has been most closely linked to body weight regulation. While a-MSH is active at this receptor and suppresses appetite after central injection, important roles for other POMC-derived products have not been excluded. The development of pharmacological agonists acting on, or mimicking, the hypothalamic melanocortinergic pathway may provide exciting opportunities for the therapy of human obesity.
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PMID:The role of melanocortin signalling in the control of body weight: evidence from human and murine genetic models. 1062 76

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

The sensory neuron-specific G protein coupled receptors (SNSRs) have been described as a family of receptors whose expression in small diameter sensory neurons in the trigeminal and dorsal root ganglia suggests an implication in nociception. To date, the physiological function(s) of SNSRs remain unknown. Hence, the aim of the present study was to determine the effects of rat SNSR1 activation on nociception in rats. The pharmacological characterization of rat SNSR1 was initially performed in vitro to identify a specific ligand, which could be used subsequently in the rat for physiological testing. Among all ligands tested, gamma2-MSH was the most potent at activating rat SNSR1. Structure-activity relationship studies revealed that the active moiety recognized by rat SNSR1 was the C-terminal part of gamma2-MSH. The radiolabeled C-terminal part of gamma2-MSH, gamma2-MSH-6-12, bound with high affinity to membranes derived from rat skin and spinal cord, demonstrating the presence of receptor protein at both the proximal and distal terminals of dorsal root ganglia. To investigate the physiological role of SNSR, specific ligands to rat SNSR1 were tested in behavioral assays of pain sensitivity in rats. Selective rat SNSR1 agonists produced spontaneous pain behavior, enhanced heat and mechanical sensitivity when injected intradermally, and heat hypersensitivity when injected centrally, consistent with the localization of rat SNSR1 protein at central and peripheral sites. Together, these results clearly indicate that the SNSR1 plays a role in nociception and may provide novel therapeutic opportunities for analgesia.
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PMID:Sensory neuron-specific receptor activation elicits central and peripheral nociceptive effects in rats. 1511 1

The finding that sensory neuron-specific G-protein-coupled receptor mRNA is solely expressed in small primary sensory neurons suggests involvement of the receptor in nociceptive modulation. The present study was designed to assess effects of intrathecal administration of bovine adrenal medulla 8-22 and (Tyr6)-gamma2-MSH-6-12, selective sensory neuron-specific receptor agonists, on nocifensive behaviors and expression of spinal c-Fos-like immunoreactivity evoked by intraplantar injection of 2.5% formalin in rats. The agonists were administered 10 min before (pretreatment) and/or after (post-treatment) injection of formalin. Pretreatment with bovine adrenal medulla 8-22 dose-dependently (3, 10 and 30 nmol) decreased time lifting and licking the paw mainly in the second phase. Intrathecal bovine adrenal medulla 8-22 (30 nmol) remarkably suppressed nocifensive behaviors in the first and second phases and the expression of formalin-evoked c-Fos-like immunoreactivity in laminae I-II and V-VI of the spinal dorsal horn at L4-5. Moreover, naloxone (20 microg, intrathecal) failed to antagonize the inhibitory effects of bovine adrenal medulla 8-22. Post-treatment with bovine adrenal medulla 8-22 also exerted inhibition on the second phase behaviors in a dose-dependent manner with a similar efficacy observed in pretreatment groups. Furthermore, post-treatment with (Tyr6)-gamma2-MSH-6-12 (0.5, 1.5 and 5 nmol) also suppressed formalin-evoked nocifensive behaviors in the second phase and c-Fos-like immunoreactivity in the spinal dorsal horn similar with bovine adrenal medulla 8-22. Our results suggest that sensory neuron-specific receptor may play an important role in modulation of spinal nociceptive transmission. This is the first to demonstrate that activation of sensory neuron-specific receptor produces analgesia in the persistent pain model.
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PMID:Intrathecal sensory neuron-specific receptor agonists bovine adrenal medulla 8-22 and (Tyr6)-gamma2-MSH-6-12 inhibit formalin-evoked nociception and neuronal Fos-like immunoreactivity in the spinal cord of the rat. 1671 12

Adrenocorticotropin (ACTH) and alpha-melanocyte stimulating hormone (alpha-MSH) are peptides which present many physiological effects related to pigmentation, motor and sexual behavior, learning and memory, analgesia, anti-inflammatory and antipyretic processes. The 13 amino acid residues of alpha-MSH are the same initial sequence of ACTH and due to the presence of a tryptophan residue in position 9 of the peptide chain, fluorescence techniques could be used to investigate the conformational properties of the hormones in different environments and the mechanisms of interaction with biomimetic systems like sodium dodecyl sulphate (SDS) micelles, sodium dodecyl sulphate-poly(ethylene oxide) (SDS-PEO) aggregates and neutral polymeric micelles. In buffer solution, fluorescence parameters were typical of peptides containing tryptophan exposed to the aqueous medium and upon addition of surfactant and polymer molecules, the gradual change of those parameters demonstrated the interaction of the peptides with the microheterogeneous systems. From time-resolved experiments it was shown that the interaction proceeded with conformational changes in both peptides, and further information was obtained from quenching of Trp fluorescence by a family of N-alkylpyridinium ions, which possess affinity to the microheterogeneous systems dependent on the length of the alkyl chain. The quenching of Trp fluorescence was enhanced in the presence of charged micelles, compared to the buffer solution and the accessibility of the fluorophore to the quencher was dependent on the peptide and the alkylpyridinium: in ACTH(1-21) highest collisional constants were obtained using ethylpyridinium as quencher, indicating a location of the residue in the surface of the micelle, while in alpha-MSH the best quencher was hexylpyridinium, indicating insertion of the residue into the non-polar region of the micelles. The results had shown that the interaction between the peptides and the biomimetic systems where driven by combined electrostatic and hydrophobic effects: in ACTH(1-24) the electrostatic interaction between highly positively charged C-terminal and negatively charged surface of micelles and aggregates predominates over hydrophobic interactions involving residues in the central region of the peptide; in alpha-MSH, which presents one residual positive charge, the hydrophobic interactions are relevant to position the Trp residue in the non-polar region of the microheterogeneous systems.
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PMID:Interaction of adrenocorticotropin peptides with microheterogeneous systems--a fluorescence study. 1901 30

Prevention of opiate tolerance is a critical issue in pain management. The present study was designed to characterize the pharmacological properties of sensory neuron-specific receptors (SNSR; also known as Mas-related gene receptors, or Mrg) for their modulation in the development of morphine tolerance and to investigate the underlying mechanism(s). Daily coadministration of the SNSR agonist BAM8-22 at a dose of 0.01 or 0.001, but not 1.0, nmol with morphine (intrathecally, or i.t., 20 microg/day) for 6 days significantly decreased the development of morphine tolerance. Coadministration of BAM8-22 (i.t., 1.0 nmol) on days 1, 3, and 5 completely blocked tolerance to morphine-induced analgesia. Intermittent coadministration of the structurally dissimilar SNSR agonist (Tyr(6))-2-MSH-6-12 (MSH; 5 nmol) also produced similar modulation. Chronic administration of morphine (20 microg, i.t.) increased expression of neuronal nitric oxide synthase (nNOS) and calcitonin gene-related peptide (CGRP) in superficial layers of the spinal cord and dorsal root ganglia. All these increases were abolished when BAM8-22 or MSH was intermittently coadministered. Furthermore, intermittent administration of BAM8-22 inhibited morphine-induced increase in protein kinase C gamma (PKC gamma) in both membrane and cytosol of spinal dorsal horn neurons. These results suggest that moderate activation of SNSR modulated morphine tolerance by inhibition of the PKC signaling pathway, leading to abolishment of enhancement of nNOS and CGRP. As SNSR are uniquely located ina subset of small-sized neurons in dorsal root and trigeminal ganglia, intermittent combination of SNSR agonist could be a promising adjunct for sustained use of opiates without central nervous system side effects.
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PMID:Modulation of sensory neuron-specific receptors in the development of morphine tolerance and its neurochemical mechanisms. 2056 89

[Tyr(6)]-gamma2-MSH(6-12) with a short effecting time of about 20 min is one of the most potent rMrgC receptor agonists. To possibly increase its potency and metabolic stability, a series of analogues were prepared by replacing the Tyr(6) residue with the non-canonical amino acids 3-(1-naphtyl)-L-alanine, 4-fluoro-L-phenylalanine, 4-methoxy-L-phenylalanine and 3-nitro-L-tyrosine. Dose-dependent nociceptive assays performed in conscious rats by intrathecal injection of the MSH peptides showed [Tyr(6)]-gamma2-MSH(6-12) hyperalgesic effects at low doses (5-20 nmol) and analgesia at high doses (100-200 nmol). This analgesic activity is fully reversed by the kyotorphin receptor-specific antagonist Leu-Arg. For the two analogues containing in position 6, 4-fluoro-L-phenylalanine and 3-nitro-L-tyrosine, a hyperalgesic activity was not observed, while the 3-(1-naphtyl)-L-alanine analogue at 10 nmol dose was found to induce hyperalgesia at a potency very similar to gamma2-MSH(6-12), but with longer duration of the effect. Finally, the 4-methoxy-L-phenylalanine analogue (0.5 nmol) showed greatly improved hyperalgesic activity and prolonged effects compared to the parent [Tyr(6)]-gamma2-MSH(6-12) compound.
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PMID:Dual effects of [Tyr(6)]-gamma2-MSH(6-12) on pain perception and in vivo hyperalgesic activity of its analogues. 2062 98


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