A COMBINATION OF PALYTOXIN WITH 1-OLEOYL-2-ACETYL-GLYCEROL (OAG) OR INSULIN OR INTERLEUKIN-1 SYNERGISTICALLY STIMULATES ARACHIDONIC-ACID METABOLISM, BUT COMBINATIONS OF 12-O-TETRADECANOYL-PHORBOL-13-ACETATE (TPA)-TYPE TUMOR PROMOTERS WITH OAG DO NOT

The combination of palytoxin and 1-oleoyl-2-acetyl-glycerol (OAG) synergistically stimulates production of 6-keto-PGF1.alpha. and PGF2.alpha. by rat liver cells (the C-9 cell line). In contrast, the combination of 12-O-tetradecanoylphorbol-13-acetate (TPA)-type tumor promoters (TPA, dihydroteleocidin B, aplysiatoxin, phorbol-12,13-didecanoate) and OAG does not. Production of 6-keto-PGF1.alpha. by palytoxin added with recombinant murine interleukin-1 (IL-1) or with insulin is also greater than the sum of the two effects taken independently. Palytoxin and OAG individually stimulate the release for radiolabeled compounds from the rat liver cells pre-labeled with [3H]arachidonic acid and also act synergistically to release labeled metabolites. After separation by h.p.l.c., these materials co-chromatograph with authentic 6-keto-PGF1.alpha. and arachidonic acid. The synergistic stimulation by palytoxin and OAG is biphasic; a rapid synergistic production of 6-keto-PGF1.alpha. or release of radiolabel from [3H]arachidonic acid prelabeled cells is followed, after .apprx. 2-4 h, by a prolonged synergistic response.