YFa, a chimeric opioid peptide, induces kappa-specific antinociception with no tolerance development during 6 days of chronic treatment

Journal of Neuroscience Research
Ishwar Dutt VatsSantosh Pasha

Abstract

Our previous study showed that YGGFMKKKFMRFamide (YFa), a chimeric peptide of Met-enkephalin, and Phe-Met-Arg-Phe-NH2 induced naloxone-reversible antinociception and attenuated the development of tolerance to morphine analgesia. In continuation, the present study investigated which specific opioid receptors-mu, delta or kappa-mediate the observed YFa antinociception pharmacologically using specific antagonists and whether chronic administration of YFa at 26.01 micromol/kg per day induces tolerance and its effect on the expression of mu and kappa opioid receptors from day 4 to day 6, with endomorphine-1 (EM-1) and saline taken as positive and negative controls, respectively. Quantitative differential expression analysis was carried out by real-time reverse-transcriptase polymerase chain reaction, and the corresponding changes in protein levels were assessed by Western blot. A pharmacological investigation revealed that nor-binaltorphimine, a specific kappa opioid receptor-1 (KOR1) antagonist, completely antagonized the antinociception induced by 39.01 micromol/kg of YFa. Importantly, its chronic intraperitoneal administration did not result in significant tolerance over 6 days, whereas EM-1 induced significant tolerance after da...Continue Reading

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Citations

Nov 24, 2011·World Journal of Gastroenterology : WJG·Krishan KumarSantosh Pasha
Dec 17, 2011·Journal of Molecular Graphics & Modelling·Mahesh Chandra PatraMadhu Chopra
Jan 15, 2013·Drug Discovery Today. Technologies·Jane V Aldrich, Jay P McLaughlin
Oct 2, 2009·Peptides·Richard J Bodnar
Jan 24, 2016·Chemical Biology & Drug Design·Annu MudgalSantosh Pasha
Oct 5, 2010·European Journal of Pharmacology·Krishan KumarSantosh Pasha
Oct 22, 2011·ACS Chemical Biology·B Ruthrotha SelviTapas K Kundu

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