Activation of the kappa-opioid receptor in Caco-2 cells decreases interleukin-8 secretion.
The immunomodulatory effects of kappa-opioid agonists at the intestinal epithelial level are not well characterized. In the present study, we determined that Caco-2 cells express the kappa-opioid receptor and its activation by trans-(+/-)-3,4-dichloro-N-methyl-N[2-(1-pyrolidinyl)cyclohexyl]benzeneacetamide methanesulfonate (U-50488) leads to decreased interleukin-8 secretion in the presence of interleukin-1beta. These effects were detected over a wide range (10 nM-50 microM) of U-50488 concentrations and were reversible using the kappa-opioid receptor antagonist nor-binaltorphimine. Our data suggest that activation of kappa-opioid receptors on Caco-2 cells decreases interleukin-8 secretion and thus may alter the chemotactic stimulus at the epithelial level.
Neudeck
Brien L
BL
University of Wisconsin School of Pharmacy, 777 Highland Avenue, Madison, WI 53705-2222, USA. blneudeck@pharmacy
Loeb
Jennifer
J
Buck
Jessica
J
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology*; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D018938:Caco-2 Cells; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism*; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000037:antagonists & inhibitors; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000276:Adjuvants, Immunologic; D007375:Interleukin-1; D016209:Interleukin-8; D017473:Receptors, Opioid, kappa; C051843:binaltorphimine; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer