Arachidonic acid regulation of prostanoid synthesis in macrophages

The dynamics of prostaglandin (PG) E-2 synthesis by mouse peritoneal macrop hages during the delivery of the basic substrate, arachidonic acid (AA), fr om different sources to the enzyme system of the cells was investigated. Th e dynamics of PGE(2) synthesis in these cells was studied both after additi on of exogenous AA and after stimulating the liberation of AA from intracel lular pools with the calcium ionophore A23187. The kinetics of PGE(2) synth esis when AA was supplied from intracellular and extracellular sources were absolutely different. PGE(2) metabolism and the inactivation of the key en zyme of PG synthesis (PGH-synthase) during the reaction may be the regulati ng factors in the kinetics of PGE(2) synthesis in the cells. For the differ ent sources of AA in the cells, the rate constants of PGE(2) consumption (k (2)) and PGH-synthase inactivation in the course of the reaction (k(in)) we re calculated. The experimentally determined value of the apparent rate con stant k(in) was identical to the theoretically calculated k(in) value for t he case when AA was provided from an intracellular source. An observed dece leration in the PGE(2) synthesis kinetics from exogenous AA is characterize d by a 10-fold drop in the apparent k(in) and k(2) values. The possibility of prostanoid synthesis regulation at the level of the traditional, constit utive isoenzyme PGH-synthase-l is discussed.