Met-enkephalin (ME) exerts a bimodal effect on functional activities of rat peritoneal macrophages (PM); in a range of low concentration (10(-9)-10(-7)M) antibody dependent cellular cytotoxicity (ADCC) was markedly stimulated with a simultaneous decrease of Fc gamma receptor (Fc gamma R) medicated phagocytosis while the opposite was observed at 10(-6)-10(-5)M concentrations. Studying the possible underlying mechanism(s) the followings were recorded: (1) ME in all applied concentrations induced an early Na+ influx which was followed by a Ca2+ efflux in the range of low concentrations. In the range of high concentrations Na+ influx was accompanied by a Ca2+ influx. (2) ME at 10(-8) M concentration induced a rise in cGMP level with a plateau in the 60-120th min of incubation. This effect was prevented by 10(-5) M of naloxone. At 10(-6) M concentration a transient rise of cAMP level was recorded which was not affected by naloxone. (3) Verapamil in 10(-6) M abolished both the Ca2+ influx and the rise in cAMP level induced by 10(-6)-10(-5) M ME but not the rise in cGMP level induced by lower ME concentrations. (4) cAMP elevation by high ME concentrations was abolished by enkephalinase inhibitory puromycin. (5) PM-enkephalinase as assessed by the cleavage of fluorogenic substrate L-alanine beta naphthylamide (ABNA), was inhibited by 10(-6)-10(-5) M of ME. This inhibition was abolished by verapamil, but not affected by naloxone. In the range of low concentrations ME appears to act on specific delta opioid receptors and its action is positively coupled to guanylate cyclase. In relatively higher concentrations ME-action is not mediated by specific delta opioid receptors and it appears to involve Ca2+ influx, adenylate cyclase activation as well as the processing of hormone by PM-enkephalinase.
Since the turn of the century, studies have been carried out showing that the omentum contains a factor which enhances revascularization of ischemic tissues. This study was conducted for a period of 3 months and was designed to evaluate the effect of an omental lipid fraction on neovascularization of autotransplanted spleen chips in dogs. Twelve dogs underwent splenectomy and autotransplantation of 5 splenic chips into an omental pouch. In 4 dogs, the splenic chips were immersed in omental angiogenic lipid factor (OAF), while on another 4 dogs, an intramuscular injection of 4 cm3 of OAF was given each day for 7 days postoperatively. A further 4 dogs were not given any of the above treatments (control group). Serial angiographies and histologic examinations demonstrated better neovascularization and regeneration of the transplanted spleen in the dogs from the immersion plus injection group. These data suggest that the omental lipid fraction contains a factor which induces a better regeneration of splenic transplants.
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