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Measurement of Smooth Muscle Function in the Isolated Tissue Bath-applications to Pharmacology Research
Published on: January 19, 2015
Tachykinin receptor expression and function in human esophageal smooth muscle
Jason R Kovac1, Tom Chrones, Harold G Preiksaitis
1Department of Physiology and Pharmacology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada N6A 5C1.
Summary
Tachykinins directly contract human esophageal smooth muscle via NK1, NK2, and NK3 receptors. This involves calcium release and influx, suggesting new therapeutic targets for esophageal motility disorders.
Area of Science:
- Gastroenterology
- Pharmacology
- Physiology
Background:
- Tachykinins are neurotransmitters in the gut.
- Their role in human esophageal smooth muscle contraction is unclear.
- Understanding these mechanisms is crucial for treating esophageal motility disorders.
Purpose of the Study:
- To characterize tachykinin signaling pathways in human esophageal smooth muscle.
- To identify the specific tachykinin receptors involved.
- To elucidate the cellular mechanisms of tachykinin-induced contraction.
Main Methods:
- Functional assays: tension recordings and isolated cell studies.
- Molecular biology: RT-PCR and immunoblotting for receptor expression.
- Electrophysiology: patch-clamp studies for membrane currents.
- Intracellular calcium imaging.
Main Results:
- Mammalian tachykinins (substance P, NKA, NKB) caused concentration-dependent esophageal smooth muscle contractions.
- Receptors NK1, NK2, and NK3 were identified on smooth muscle cells.
- Contraction involved intracellular calcium release and L-type calcium channel influx.
- NK2 receptor blockade significantly reduced tachykinin-evoked responses.
- Neurokinin A (NKA) activated a nonselective cation current (I(NSC)).
Conclusions:
- Tachykinins directly stimulate human esophageal smooth muscle contraction via NK1, NK2, and NK3 receptors.
- Signaling involves calcium release, I(NSC) activation, and calcium influx.
- These findings reveal novel tachykinin signaling pathways in the esophagus.
- Excitatory tachykinin pathways are potential targets for treating esophageal dysmotility.
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