The g2-MSH peptide mediates a central analgesic effect via a GABA-ergic mechanism that is independent from activation of melanocortin receptors

Kluša, Vija; Germane, S. K.; Svirskis, Šimons; Opmane, B; Wikberg, Jarl E. S.

doi:10.1054/npep.2000.0843

Cited by 16 publications

(5 citation statements)

References 22 publications

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“…Salvigenin, rosmanol and cirsimaritin exerted significant antinociceptive effects in both hot plate and tail immersion tests at the dose level of 10-100 mg/kg. The cellular and neural mechanisms underlying pain responses elicited involves interplay of a number of neurotransmitters and ion channels [35,36], and the central analgesic effects of salvigenin, rosmanol and cirsimaritin were not antagonized by the opioid receptor antagonist naloxone. This indicates that the central analgesic effects of salvigenin, rosmanol and cirsimaritin may be exerted via one or more of several proposed nonopioid mechanisms such as blockade of voltagegated Na + channels, activation of the noradrenergic inhibitory system, enhancement of GABAergic and/or serotonergic systems [34].…”

Section: Discussionmentioning

confidence: 99%

Antidepressant, Anxiolytic and Antinociceptive Activities of Constituents from Rosmarinus Officinalis

et al. 2015

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Purpose. Rosmarinus officinalis, traditionally known as rosemary, has been widely used in traditional medicines and has long been known as the herb of remembrance. However, few studies have investigated the effects of non-volatile components of rosemary on central nervous system function. Methods. Fractionation of R. officinalis led to the isolation of salvigenin, rosmanol and cirsimaritin, which were investigated in mouse models of acute toxicity, antinociception (tail immersion and hot plate tests), depression (tail suspension and forced swim tests) and anxiety (elevated plus maze and light/dark box paradigms). Results. Rosmanol, cirsimaritin and salvigenin were not found to exhibit any signs of acute toxicity (50-200 mg/kg), but elicited antinociceptive, antidepressant and anxiolytic activities. Conclusion. Rosmanol, cirsimaritin and salvigenin, all previously shown to have biphasic modulation of GABAA receptors, demonstrated CNS activity in mouse models of antinociception, antidepressant and anxiolysis. The anxiolytic activity of all three compounds was not ameliorated by flumazenil, but was inhibited by pentylenetetrazol, suggesting a mode of action via GABAA receptors at a site other than the high affinity benzodiazepine binding site. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

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Section: Discussionmentioning

confidence: 99%

Antidepressant, Anxiolytic and Antinociceptive Activities of Constituents from Rosmarinus Officinalis

et al. 2015

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“…In contrast, a melanocortin receptor agonist has the opposite effect [55]. Interestingly, γ subtype of MSH acts via γ‐amino butyric acid (GABA) receptor pathway rather than melanocortin pathway and has analgesic activity [56]. Even more intriguing is the interaction between melanocortins and opioids.…”

Section: Target Sites and Molecules For Gene Therapy Of Chronic Neuromentioning

confidence: 99%

Gene Therapy for Chronic Neuropathic Pain: How Does It Work and Where Do We Stand Today?

Kumar¹,

Ruchi²,

James³

et al. 2011

Pain Med

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Objectives. Chronic neuropathic pain has been an enigma to physicians and researchers for decades. A better understanding of its pathophysiology has given us more insight into its various mechanisms and possible treatment options. We now have an understanding of the role of various ionic channels, biologically active molecules involved in pain, and also the intricate pain pathways where possible interventions might lead to substantial pain relief. The recent research on laboratory animals using virus-based vectors for gene transfer at targeted sites is very promising and may lead to additional human clinical trials. However, one needs to be aware that this "novel" approach is still in its infancy and that many of its details need to be further elucidated. The purpose of this article is to thoroughly review the current available literature and analyze the deficiencies in our current knowledge.Design. Literature review.Methods. After an extensive online literature search, a total of 133 articles were selected to synthesize a comprehensive review about chronic neuropathic pain and gene therapy in order to understand the concepts and mechanisms.Results. Most of the studies have shown benefits of gene therapy in animal models, and recently, phase 1 human trials using herpes simplex virus vector have started for intractable cancer pain.Conclusion. Although animal data have shown safety and efficacy, and initial human trials have been promising, additional studies in humans are required to more completely understand the actual benefits and risks of using gene therapy for the treatment of chronic neuropathic pain.

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“…In recent years, different investigators have found pharmacological evidence for the existence in various other biological response systems of other receptors with high affinity for one or more of the γ‐MSH peptides and different from the MC3R or other known MCRs 48–50. However, the pharmacological characteristics of these receptors are different from those of the γ‐MSH receptor in GH3 cells.…”

Section: Receptors and Signal Transductionmentioning

confidence: 99%

“…N‐POMC is also called pro‐γ‐MSH 1–6. The C‐terminal end of N‐POMC is cleaved as γ3‐MSH between the two basic amino acids Arg49 and Lys50, but mainly in the intermediate lobe, and may be further processed to γ2‐ and γ1‐MSH, the latter being a C‐amidated peptide. The peptides have been immunologically detected in the pituitary 3,4,7,8.…”

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confidence: 99%

γ‐MSH Peptides in the Pituitary

Denef

Lü

Swinnen

2003

Annals of the New York Academy of Sciences

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The melanocortin (MC) gamma3-MSH is believed to signal through the MC3 receptor. We showed that it induces a sustained increase in intracellular free calcium levels ([Ca(2+)](i)) in a subpopulation of pituitary cells. Most of the cells responding to gamma3-MSH express more than one pituitary hormone mRNA. The effect of gamma3-MSH is blocked by SHU9119, a MC3R and MC4R antagonist, in only 50% of the responsive cells, suggesting that in half of these cells the mediating receptor is not the MC3R. Low picomolar doses of gamma3-MSH increase [Ca(2+)](i) in the growth hormone (GH)- and prolactin (PRL)-secreting GH3 cell line. gamma2-MSH and alpha-MSH display a similar effect. SHU9119 does not affect the gamma3-MSH-induced [Ca(2+)](i) response. MTII, a potent synthetic agonist of the MC3R, MC4R, and MC5R, also shows no or low potency in increasing [Ca(2+)](i). By means of RT-PCR, the mRNA of the MC2R, MC3R, and MC4R receptors is undetectable. Experiments testing gamma2-MSH analogues with single alanine replacements show that, unlike the classic MCRs, the His(5)-Phe(6)-Arg(7)-Trp(8) sequence in gamma2-MSH is not a core sequence for activating the gamma-MSH receptor in GH3 cells, whereas Met(3) is essential. Low nanomolar doses of gamma-MSH increase intracellular cAMP levels. Blockade of protein kinase A abolishes the [Ca(2+)](i) responses to gamma3-MSH. gamma2-MSH increases binding of [S(35)]GTPgammaS to membrane preparations of GH3 cells. The pharmacological characteristics of gamma-MSH peptides and analogues on [Ca(2+)](i) and the signal-transduction pathways present strong evidence for the expression of a hitherto uncharacterized gamma-MSH receptor in GH3 cells, belonging to the G protein-coupled receptor family.

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The g2-MSH peptide mediates a central analgesic effect via a GABA-ergic mechanism that is independent from activation of melanocortin receptors

Cited by 16 publications

References 22 publications

Antidepressant, Anxiolytic and Antinociceptive Activities of Constituents from Rosmarinus Officinalis

Antidepressant, Anxiolytic and Antinociceptive Activities of Constituents from Rosmarinus Officinalis

Gene Therapy for Chronic Neuropathic Pain: How Does It Work and Where Do We Stand Today?

γ‐MSH Peptides in the Pituitary

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