Platelet-activating factor contracts guinea pig esophageal muscularis mucosae by stimulating extracellular Ca2+ influx through diltiazem-insensitive Ca2+ channels

Platelet-activating factor (PAF) is expected to increase esophageal motility. However, to the best of our knowledge, this has not been examined. Thus, we investigated the contractile effects of PAF on guinea pig (GP) esophageal muscularis mucosae (EMM) and the extracellular Ca²⁺ influx pathways responsible. PAF (10⁻⁹–10⁻⁶ M) contracted EMM in a concentration-dependent manner. PAF (10⁻⁶ M)-induced contractions were almost completely suppressed by apafant (a PAF receptor antagonist, 3 × 10⁻⁵ M). In EMM strips, PAF receptor and PAF-synthesizing/degrading enzyme mRNAs were detected. PAF (10⁻⁶ M)-induced contractions were abolished by extracellular Ca²⁺ removal but were not affected by diltiazem [a voltage-dependent Ca²⁺ channel (VDCC) inhibitor, 10⁻⁵ M]. PAF (10⁻⁶ M)-induced contractions in the presence of diltiazem were significantly suppressed by LOE-908 [a receptor-operated Ca²⁺ channel (ROCC) inhibitor, 3 × 10⁻⁵ M], SKF-96365 [an ROCC and store-operated Ca²⁺ channel (SOCC) inhibitor, 3 × 10⁻⁵ M], and LOE-908 plus SKF-96365. Among the tested ROCC/SOCC-related mRNAs, Trpc3, Trpc6, and Trpv4/Orai1, Orai3, and Stim2 were abundantly expressed in EMM strips. These results indicate that PAF potently induces GP EMM contractions that are dependent on extracellular Ca²⁺ influx through ROCCs/SOCCs, and VDCCs are unlikely to be involved.