Histamine and prostaglandin interaction in the central regulation of ACTH secretion

Since prostaglandins (PGs) and histamine (HA) seem to be involved in the activation of the hypothalamic-pituitary-adrenal axis following immunochallenges with lipopolysaccharide (LPS) endotoxin and cytokines, we investigated whether the histaminergic and eicosanoid systems in the male rat brain interact in their regulation of ACTH secretion. The PG synthesis inhibitor indomethacin (10 mg/kg i.p.) attenuated the ACTH response to LPS (10 mu g/kg i.p.) and HA (30 mu g i.c.v.). Infusion of PGE(1), PGE(2) or PGF(2 alpha) (1 and/or 5 mu g infused intracerebroventricularly) stimulated ACTH secretion. The ACTH response to PGE(1) was inhibited by the HA synthesis inhibitor alpha-fluoromethylhistidine and the H-1 receptor antagonist mepyramine (MEP) but not the H-2 receptor antagonist cimetidine (CIM). Neither MEP nor CIM affected the ACTH response to PGE(2). MEP and CIM attenuated the ACTH response induced by PGF(2 alpha). The findings indicate that HA and some PGs in the brain interact in their stimulatory regulation of ACTH secretion. Such an interaction may also be involved in their mediation of the ACTH response to immunochallenges.