Impaired coupling of naloxone sensitive opiate receptors to adenylate cyclase in PMNLs of aged male subjects.
Met-enkephalin (Met-enk) in 10(-9)-10(-7) M concentrations enhanced the extracellular cytotoxicity of polymorphonuclear leukocytes (PMNL) of young adult humans partly by stimulation of the "respiratory burst" in these cells. Meanwhile adenylate cyclase was inhibited and guanylate cyclase was stimulated. All the observed effects were abolished by 10(-5) M naloxone. On the other hand, a positive receptor coupling to adenylate cyclase was found when Met-enk was added in higher (10(-6)-10(-5) M) concentrations to PMNLs. The elevated cAMP level resulted in decreased extracellular cytotoxicity of PMNLs by a naloxone insensitive way. In PMNLs obtained from healthy aged male subjects, Met-enk induced in all of the applied concentrations an increased cAMP level and no change in cGMP level, with subsequent decrease of cytotoxicity, i.e. an impaired negative coupling of naloxone sensitive opiate receptors was detected with aging.
Fulop
T
T
First Department of Medicine, University Medical School, Debrecen, Hungary.
Kekessy
D
D
Foris
G
G
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004744:Enkephalin, Methionine / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009270:Naloxone / Q000494:pharmacology*; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D011957:Receptors, Opioid / Q000378:metabolism*
D011957:Receptors, Opioid; D009270:Naloxone; D004744:Enkephalin, Methionine; D006861:Hydrogen Peroxide; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D006152:Cyclic GMP