Arachidonic Acid Regulation of Prostanoid Synthesis in Macrophages

M. V. Gonchar, M. G. Sergeeva^*, A. T. Mevkh, and S. D. Varfolomeyev

Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119899 Russia; fax: (095) 939-3181; E-mail: sergeeva@libro.genebee.msu.su

^* To whom correspondence should be addressed.

Received April 20, 1998

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The dynamics of prostaglandin (PG) E₂ synthesis by mouse peritoneal macrophages during the delivery of the basic substrate, arachidonic acid (AA), from different sources to the enzyme system of the cells was investigated. The dynamics of PGE₂ synthesis in these cells was studied both after addition of exogenous AA and after stimulating the liberation of AA from intracellular pools with the calcium ionophore A23187. The kinetics of PGE₂ synthesis when AA was supplied from intracellular and extracellular sources were absolutely different. PGE₂ metabolism and the inactivation of the key enzyme of PG synthesis (PGH-synthase) during the reaction may be the regulating factors in the kinetics of PGE₂ synthesis in the cells. For the different sources of AA in the cells, the rate constants of PGE₂ consumption (k₂) and PGH-synthase inactivation in the course of the reaction (k_in) were calculated. The experimentally determined value of the apparent rate constant k_in was identical to the theoretically calculated k_in value for the case when AA was provided from an intracellular source. An observed deceleration in the PGE₂ synthesis kinetics from exogenous AA is characterized by a 10-fold drop in the apparent k_in and k₂ values. The possibility of prostanoid synthesis regulation at the level of the traditional, constitutive isoenzyme PGH-synthase-1 is discussed.

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KEY WORDS: arachidonic acid, prostaglandin E₂, prostaglandin H-synthase, peritoneal macrophages

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