Enkephalins modify granulocyte-endothelial interactions by stimulating prostacyclin production.
Granulocyte (PMN)-endothelial interactions have been implicated in the primary events of vascular injury and atherogenesis. We now present data which show that endogenous opioid peptides, e.g. enkephalins (ENK), dampen immune-triggered, granulocyte-induced endothelial damage by enhancing prostacyclin production. Concurrent exposure of human umbilical vein endothelial cells (HUEC) to Met5-enkephalin increased arachidonic acid (AA, 20 muM) and thrombin (T, 10 U/ml) induced 6-keto-PGF1 alpha-release to respectively 197.2 +/- 28.1% and 204.1 +/- 17.8% (mean +/- SEM) of base line stimulation (p less than 0.025). The increases noted were significant at ENK-concentrations as low as 10(-12)M. Simultaneous addition of naloxone with ENK completely abolished the enhanced 6-keto-PGF1 alpha-release. Addition of a protease resistant enkephalin analogue significantly (p less than 0.01 over several different concentrations) reduced PMN adherence to HUEC; concomitantly 51Cr-leakage from HUEC that had been exposed to PMN plus activated serum complement was decreased. The even further enhanced 51Cr-leakage that occurs when platelet release products (e.g. serotonin) are included is also decreased by added enkephalin. These data suggest that endogenous neurotransmitters may affect endothelial prostaglandin metabolism, and by so doing provide a protective effect during in vitro, and perhaps in vivo, PMN mediated endothelial injury. This link between neurohumoral and inflammatory systems might enhance our understanding of stress-related phenomena in inflammation and vascular diseases.
D002448:Cell Adhesion / Q000187:drug effects; D003165:Complement System Proteins / Q000502:physiology; D004727:Endothelium / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D004744:Enkephalin, Methionine / Q000502:physiology; D004745:Enkephalins / Q000502:physiology*; D011464:Epoprostenol / Q000096:biosynthesis*; D006801:Humans; D009504:Neutrophils / Q000378:metabolism* / Q000502:physiology; D011460:Prostaglandins F / Q000096:biosynthesis; D014471:Umbilical Veins / Q000166:cytology
D004745:Enkephalins; D011460:Prostaglandins F; D004744:Enkephalin, Methionine; C027970:enkephalin, AlaNH2(5)-; D003165:Complement System Proteins; D011464:Epoprostenol; C100006:prostaglandin F1