Effects of intracerebroventricularly administered chimeric peptide of metenkephalin and FMRFa--[D-Ala2]YFa-on antinociception and its modulation in mice.
An enzymatically stable analog of YGGFMKKKFMRFamide (YFa), a chimeric peptide of metenkephalin and FMRFa, was synthesised. The antinociceptive effects of intracerebroventricular injections of this analog-[D-Ala2)]YAGFMKKKFMRFamide ([D-Ala2]YFa)-was then investigated using the mouse radiant-heat tail-flick test. [D-Ala2]YFa produced modest to good antinociception at 1, 2, and 5 microg/mouse (0.64, 1.28, and 3.22 nmol, respectively). This antinociceptive effect was completely reversed by the opioid receptor antagonist naloxone (1.5 microg/mouse: 4.12 nmol, intracerebroventricular [i.c.v.]), administered 5 min prior. Pretreatment (5 min) with either neuropeptides FF (1 microg/mouse: 0.92 nmol, i.c.v.) or FMRFa (1 microg/mouse: 1.69 nmol, i.c.v.) significantly attenuated the antinociceptive effects induced by [D-Ala2]YFa (1 microg/mouse, i.c.v.). Intracerebroventricular administration of [D-Ala2]YFa at 1 microg/mouse dose with morphine (2 microg/mouse: 5.86 nmol, i.c.v.) produced an additive antinociceptive effect, suggesting that [D-Ala2]YFa may have a modulatory effect on opioid (morphine) analgesia. These results provide further support for a role of such amphiactive sequences in antinociception and its modulation.
Gupta
S
S
Peptide Laboratory, Centre for Biochemical Technology (CSIR), Delhi, India.
Pasha
S
S
Gupta
Y K
YK
Bhardwaj
D K
DK
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004347:Drug Interactions / Q000502:physiology; D004744:Enkephalin, Methionine / Q000494:pharmacology; D019835:FMRFamide / Q000494:pharmacology; D007276:Injections, Intraventricular; D051379:Mice; D008815:Mice, Inbred Strains; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects* / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D010147:Pain Measurement / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000494:pharmacology*
C436407:Ala2-YAGFMKKKFMRFamide; D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D009842:Oligopeptides; D011993:Recombinant Fusion Proteins; D009270:Naloxone; D004744:Enkephalin, Methionine; D019835:FMRFamide; D009020:Morphine; C053651:phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide