Morphine-induced changes in the activity of proopiomelanocortin and prodynorphin systems in zymosan-induced peritonitis in mice.
We have shown that supplementation of proinflammatory agent with a high dose of morphine not only abolishes inflammation-related pain symptoms but also inhibits influx of leukocytes to the inflamed peritoneal cavity. Present investigations focused on effects of morphine on proopiomelanocortin and prodynorphin systems during zymosan-induced peritonitis. Males of SWISS mice were ip injected with zymosan (Z, 40 mg/kg) or zymosan with morphine (ZM, 20 mg/kg). At time 0 (controls) and 4 and 24h after stimulation, peritoneal leukocytes (PTLs) were counted, PTL levels of opioid peptides (beta-endorphin and dynorphin) measured by radioimmunoassays, while mRNAs coding their respective precursors (POMC and PDYN) and receptors (MOR and KOR) determined by QRT-PCR. Influx of inflammatory PTLs, mainly PMNs, was significantly delayed by morphine co-injection. Total levels of beta-endorphin and dynorphin corresponded with PTL numbers, while levels per cell were similar in all groups except of beta-endorphin, decreased in ZM at 4h. Levels of both peptides in peritoneal fluid were increased in Z and ZM groups at 4h, while at 24h only in case of beta-endorphin in Z group. POMC was increased only in ZM group at 4h of peritonitis, while PDYN in both Z and ZM groups at the same time. MOR mRNA was increased 24h after injection in Z and ZM groups, while KOR mRNA was similar in all groups except of decrease in Z at 24h. In conclusion, endogenous opioids and their receptors are involved in zymosan-induced peritonitis and affected in various ways by morphine co-injection.
Chadzinska
M
M
Department of Evolutionary Immunobiology, Institute of Zoology, Jagiellonian University, Cracow, Poland.
Starowicz
K
K
Scislowska-Czarnecka
A
A
Bilecki
W
W
Pierzchala-Koziec
K
K
Przewlocki
R
R
Przewlocka
B
B
Plytycz
B
B
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004745:Enkephalins / Q000378:metabolism*; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D010538:Peritonitis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D017473:Receptors, Opioid, kappa / Q000235:genetics; D017450:Receptors, Opioid, mu / Q000235:genetics; D015054:Zymosan / Q000494:pharmacology
D004745:Enkephalins; D011498:Protein Precursors; D012333:RNA, Messenger; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D011333:Pro-Opiomelanocortin; D009020:Morphine; D015054:Zymosan; C033660:preproenkephalin