Lymphokines production by concanavalin A-stimulated mouse splenocytes: modulation by Met-enkephalin and a related peptide.
Methionine-enkephalin (ME) and its synthetic congener Tyr-D-Ala-Gly-Me-Phe-Gly-NH.C3H7-iso (82/205), in a concentration-dependent biphasic manner modulated the concanavalin A (Con A)-stimulated phagocytosis-promoting (PP)-activity elaboration in the culture supernatants of mouse splenocytes in vitro. Both these peptides at 1 x 10(-5) and 1 x 10(-6) M inhibited the production of PP activity; conversely, at 1 x 10(-7)-1 x 10(-9) M they augmented it. Peptide 82/205 was nearly 1.2-fold more inhibitory and approximately 1.8-fold more potent in augmenting the PP activity elaboration. The PP activity appeared to be due to lymphokines (LK) gamma interferon and interleukin-4 as the neutralizing concentrations of monoclonal antibodies against these LK significantly (p < 0.05) inhibited it. Cycloheximide (50.0 micrograms/ml) completely inhibited the production of LK indicating their de novo synthesis. The peptides appeared to exert their inhibitory and augmenting effects via delta- and mu-opioid receptors, respectively, as pretreatment of splenocytes with 100-fold higher (1 x 10(-3) M) concentration of naloxone was required to block their inhibitory effect; the augmenting effect was blocked by 1 x 10(-5) M only. None of the peptides or naloxone could directly stimulate the splenocytes for PP-LK elaboration.
Singh
S
S
Division of Microbiology, Central Drug Research Institute, Lucknow, India.
Singh
P P
PP
Dhawan
V C
VC
Haq
W
W
Mathur
K B
KB
Dutta
G P
GP
Srimal
R C
RC
Dhawan
B N
BN
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004744:Enkephalin, Methionine / Q000494:pharmacology*; D008222:Lymphokines / Q000096:biosynthesis*; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009270:Naloxone / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology*; D010587:Phagocytosis / Q000187:drug effects*; D013154:Spleen / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D008222:Lymphokines; D009842:Oligopeptides; D003208:Concanavalin A; C089012:tyrosyl-alanyl-glycyl-(methyl)phenylalanyl-glycine-(N-isopropyl)amide; D009270:Naloxone; D004744:Enkephalin, Methionine