Abstract Previous studies identified a prostaglandin E 2 (PGE 2 ) receptor in the salivary glands of partially fed female lone star ticks, Amblyomma americanum (L.). In the present studies, protein secretion from dispersed salivary gland acini was shown to be specific for PGE 2 , as compared with PGF 2α or the thromboxane analog U-46619, in accordance with their respective binding affinities for the PGE 2 receptor. Furthermore, the selective PGE 2 EP1 receptor agonist, 17-phenyl trinor PGE 2 , was as effective as PGE 2 in stimulating secretion of anticoagulant protein. Calcium ionophore A-23187 (1 to 100 µM) stimulated secretion of anticoagulant protein in a dose-dependent manner but the voltage-gated Ca 2+ -channel blocker verapamil (1 to 1000 µM) and the receptor-mediated Ca 2+ -entry antagonist, SK&F 96365 (1 and 10 µM), and 5 mM ethylene glycol bis(β-aminoethyl ether)-N,NNЈ,NЈ-tetraacetic acid (EGTA) had no appreciable effect on inhibiting PGE 2 -stimulated secretion of anticoagulant protein. PGE 2 (0.1 µM) and the nonhydrolyzable analog of guanosine triphosphate (GTP), GTPγS (10 µM), directly activated phospholipase C (PLC) in a membraneenriched fraction of the salivary glands after PLC was first incubated with the PGE 2 EP1 receptor antagonist AH-6809, which presumably antagonized endogenous PGE 2 (0.3 µM) in the broken-cell-membrane-enriched fraction. TMB-8, an antagonist of intracellular inositol trisphosphate (IP 3 ) receptors, inhibited PGE 2 -stimulated secretion. The results support the hypothesis that PGE 2 stimulates secretion of tick salivary gland protein via a phosphoinositide signaling pathway and mobilization of intracellular Ca 2+
