Role of endogenous opioids in soman (pinacolyl methylphosphonofluoridate)-induced antinociception.
The effect of soman poisoning on the levels of methionine enkephalin and beta-endorphin in mice and rats were determined. Soman poisoning produced no significant effect on methionine enkephalin levels in the striatum of rats or mice or beta-endorphin levels in the pituitary gland of mice. In rats beta-endorphin levels were significantly reduced 24 hr post soman poisoning, but returned to control levels by 48 hr. In vitro, the hydrolysis of leucine enkephalin by aminopeptidase was virtually complete by 30 min and found to be the major route of degradation. The release of TYR-GLY-GLY in the presence or absence of puromycin (10 microM) was found to be low (less than or equal to 2.0%). A minor effect on TYR release in the presence of GLY-GLY-PHE-MET (50 microM) was insignificant. Preincubation of mouse striatum homogenates with soman (1 or 10 microM) did not inhibit the hydrolysis of leucine enkephalin. These results suggest that the long term antinociception following soman exposure is not due to either altered concentration of endogenous opioid-like substances or inhibition of the enzymes responsible for their degradation.
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010450:Endopeptidases / Q000378:metabolism; D004723:Endorphins / Q000378:metabolism*; D004743:Enkephalin, Leucine / Q000378:metabolism*; D008297:Male; D051379:Mice; D015260:Neprilysin; D010146:Pain / Q000503:physiopathology*; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D012999:Soman / Q000633:toxicity*; D001615:beta-Endorphin
D004723:Endorphins; D004743:Enkephalin, Leucine; D001615:beta-Endorphin; D012999:Soman; D010450:Endopeptidases; D015260:Neprilysin