There is an increasing body of evidence that prostanoids modulate mast cell functions and contribute to the development of allergic inflammation. The present study aimed to identify an undetermined function of prostaglandin (PG) F-2 alpha in mast cell activation and the signaling mechanism involved in it. Simultaneous quantification of prostanoids by liquid chromatography/tandem mass spectrometry revealed the constitutive release of PGF(2 alpha) thromboxane B-2, and 6-keto-PGF(1 alpha) from bone marrow-derived mast cells (BMMCs). Upon activation of BMWs by lipopolysaccharide, the cytokine production in BMMCs was enhanced when the culture was supplemented with PGF(2 alpha). However, F prostanoid receptor-a selective receptor for PGF(2 alpha)-was not detected in BMMCs. Further investigations performed using prostanoid receptor antagonists revealed an alternative mechanism wherein the receptors for PGE species-E prostanoid receptors-mediated the PGF(2 alpha) signal in BMMCs. The present study provides an insight into a novel function of PGF(2 alpha) i.e., an autocrine accelerator for mast cell activation. (C) 2008 Elsevier Inc. All rights reserved.