Blockade of analgesic effects following systemic administration of N-methyl-kyotorphin, NMYR and arginine in mice deficient of preproenkephalin or proopiomelanocortin gene

Publication date: Available online 21 July 2018Source: PeptidesAuthor(s): Hiroyuki Neyama, Yusuke Hamada, Ryoko Tsukahara, Minoru Narita, Kazuhiro Tsukamoto, Hiroshi UedaABSTRACTKyotorphin is a unique biologically active neuropeptide (L-tyrosine-L-arginine), which is reported to have opioid-like analgesic actions through a release of Met-enkephalin from the brain slices. N-methyl-L-tyrosine-L-arginine (NMYR), an enzymatically stable mimetic of kyotorphin, successfully caused potent analgesic effects in thermal and mechanical nociception tests in mice when it was given through systemic routes. NMYR analgesia was abolished in μ-opioid receptor-deficient (MOP-KO) mice, and by intracerebroventricular (i.c.v.) injection of naloxone and of N-methyl L-leucine-L-arginine (NMLR), a kyotorphin receptor antagonist. In the Ca2+-mobilization assay using CHO cells expressing Gαqi5 and hMOPr or hDOPr, however, the addition of kyotorphin neither activated MOPr-mechanisms, nor affected the concentration-dependent activation of DAMGO- or Met-Enkephalin-induced MOPr activation, and Met-enkephalin-induced DOPr activation. NMYR-analgesia was significantly attenuated in preproenkephalin (PENK)- or proopioimelanocortin (POMC)-KO mice. The systemic administration of arginine, which is reported to elevate the level of endogenous kyotorphin selectively in midbrain and medulla oblongata, pain-related brain regions, caused significant analgesia, and the analgesia was reversed by i.c.v. injection of NM...

Source: Peptides - July 21, 2018 Category: Biochemistry Source Type: research