Scientists Uncover How Inflammatory Molecule Induces Esophageal Muscle Contraction

A research team has made significant progress in understanding how platelet-activating factor (PAF), a potent inflammatory molecule, initiates contractions in the smooth muscles of the esophagus. This discovery, detailed in the recent publication of the Biological and Pharmaceutical Bulletin, could lead to innovative treatments for gastrointestinal symptoms linked with allergic reactions, asthma, and anaphylaxis.

PAF is a bioactive lipid produced by various cells, notably immune cells, during inflammatory responses. It plays critical roles in processes such as blood clotting, immune cell recruitment, and the development of allergic reactions, where it makes blood vessels more permeable and stimulates smooth muscle contractions in tissues including the lungs, intestines, and esophagus. While PAF’s function is vital for immune defense, excessive or uncontrolled activity has been associated with conditions like asthma, inflammatory bowel disease, and severe allergies.

The study, led by Dr. Keisuke Obara, Dr. Kento Yoshioka, and Professor Yoshio Tanaka from Toho University’s Department of Chemical Pharmacology, focused on how PAF causes esophageal muscle contractions in rats. Their research revealed that PAF induces calcium entry into muscle cells via three types of channels: L-type voltage-dependent calcium channels (VDCCs), receptor-operated calcium channels (ROCCs), and store-operated calcium channels (SOCCs). Notably, the researchers found that SOCCs, particularly a protein called Orai1, are the primary drivers of PAF-induced contractions. This challenges the traditional emphasis on VDCCs in smooth muscle pharmacology and opens new potential avenues for targeted therapy.

“Our findings suggest that targeting these non-traditional calcium channels could offer more effective treatment options for esophageal and broader gastrointestinal symptoms associated with allergies,” said Dr. Obara. By pinpointing specific calcium channels involved in pathological muscle contractions, new drugs could be developed to inhibit these channels precisely, reducing unwanted muscle activity while preserving normal function elsewhere.

This research advances our understanding of the molecular mechanisms underlying allergic gastrointestinal manifestations and holds promise for improving management strategies for related conditions.

Source: https://medicalxpress.com/news/2025-07-scientists-reveal-key-inflammatory-molecule.html