EVALUATION OF A C-TERMINALLY TRUNCATED CHIMERIC OPIOID PEPTIDE [DES-PHE12]YFA ON ANTINOCICEPTIVE ACTIVITY, RECEPTOR SPECIFICITY, AND RECEPTOR REGULATION ON CHRONIC ANALGESIC EFFICACY

Abstract

The physiologic function of the NPFF/FMRFa peptide group is still complex, and their exact mode of action is unclear. Structure on the current line of inquiry, our previous chore describes a couple of chimeric concepts derived Metenkephalin (Tyr-Gly-Gly-Phe-Met) and FMRFa (Phe-Met-Arg-Phe-NH2) YGGFMKKKKFMRFamide (YFa) and Y(D-Ala)GFMKKKKFMRFamide ([D-Ala2]YFa). The aforementioned hybrid peptide has been shown to induce naloxone-reversible antinociceptive effects and to reduce the onset of tolerance associated with morphine-induced analgesia. Moreover, in the presence of FMRFa and NPFF peptides, the antinociception of [D-Ala2]YFa was markedly reduced. In addition to investigating the contribution of the C terminal FMRFamide motif to trouble transition and receptor selectivity, we rationally developed and synthesized a recent analogy where the essential Phe residue from twelfth position was eliminated, YGGFMKKKFMRamide ([Des-Phe12]YFa). The present work investigates the antinociceptive potential of [Des-Phe12]YFa following intraperitoneal administration to rats, measuring using the tail-flick assay, and analysing their receptor specificity using the antagonistic target, and opioid receptor. Moreover, the efficacy of the treatment was measured throughout the duration of treatment, together with changes in opioid receptor expression evaluated using western blotting with real-time reverse transcriptase polymerase chain reaction (RTPCR). The results show that YFa has a receptor intercede, dose-dependent antinociception, although its magnitude was lower than that detected in association with the caregiver peptide YFa. Its analgesic effects remained stable, and its receptor expression was selectively increased in parallel to the same transcript and protein stages. Together, these pharmacological and molecular discoveries show that although the engineered YFa functions essentially as an opioid antagonist, the abbreviated –RFa part contributes to the overall antinociceptive profile of the amphiactive chimeric peptide.