Uncovering how a key inflammatory molecule causes esophageal smooth muscle contractions

A research group led by Dr. Keisuke Obara, Dr. Kento Yoshioka, and Professor Yoshio Tanaka from the Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toho University, has uncovered important details about how platelet-activating factor (PAF)-a powerful molecule involved in inflammation and allergic reactions-triggers contractions in the smooth muscles of the esophagus. Their findings could pave the way for new treatments targeting gastrointestinal symptoms associated with allergies, asthma, and anaphylaxis.

What is PAF?

PAF (platelet-activating factor) is a bioactive lipid molecule produced by various cells in the body, including immune cells, during inflammatory responses. It plays a major role in processes such as blood clotting, immune cell recruitment, and the onset of severe allergic reactions, including anaphylaxis, by making blood vessels more permeable and stimulating smooth muscle contraction in tissues like the lungs, intestines, and esophagus.

Although PAF is essential for immune defense, excessive or misdirected PAF activity is linked to pathological conditions such as asthma, inflammatory bowel disease, and allergic reactions that affect breathing and digestion.

Study highlights

In their study, the researchers investigated how PAF causes contractions in the esophageal smooth muscle of rats-a process that contributes to symptoms like chest tightness and difficulty swallowing during allergic episodes.

They discovered that PAF triggers calcium entry into muscle cells through three distinct types of calcium channels:

  • L-type voltage-dependent calcium channels (VDCCs),
  • Receptor-operated calcium channels (ROCCs),
  • Store-operated calcium channels (SOCCs).

Importantly, the study revealed that non-VDCC channels-particularly a protein called Orai1 that forms SOCCs-are the main drivers of PAF-induced muscle contraction in the esophagus. This challenges the traditional focus on VDCCs in smooth muscle pharmacology.

Our findings suggest that targeting these non-traditional calcium channels could offer more effective treatments for esophageal and gastrointestinal symptoms seen in allergic conditions."

Dr. Keisuke Obara, lead researcher

Implications for future therapies

By better understanding which calcium channels PAF uses to trigger muscle contraction, the study lays the groundwork for developing new drugs that can more precisely block unwanted muscle activity without affecting normal muscle function elsewhere.

Source:
Journal reference:

Obara, K., et al. (2025). Pharmacological Characteristics of Extracellular Ca2+ Influx Pathways Responsible for Platelet-Activating Factor-Induced Contractions in Rat Esophagus Smooth Muscle: Involvement of L-Type, Receptor-Operated, and Store-Operated Ca2+ Channels. Biological and Pharmaceutical Bulletin. doi.org/10.1248/bpb.b25-00233.

Comments

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
Post a new comment
Post

While we only use edited and approved content for Azthena answers, it may on occasions provide incorrect responses. Please confirm any data provided with the related suppliers or authors. We do not provide medical advice, if you search for medical information you must always consult a medical professional before acting on any information provided.

Your questions, but not your email details will be shared with OpenAI and retained for 30 days in accordance with their privacy principles.

Please do not ask questions that use sensitive or confidential information.

Read the full Terms & Conditions.

You might also like...
Mount Sinai launches AI center to revolutionize small molecule drug discovery