Topical ATP application in the peripheral swallowing-related regions facilitates triggering of the swallowing reflex involving P2×3 receptors.

Abstract

The swallowing reflex is a critical component of the digestive process, triggered when food or liquids pass from the oral cavity to the oesophagus. Although adenosine triphosphate (ATP) is involved in various physiological processes, its potential to trigger the swallowing reflex has not been fully explored. This study investigated the ability of ATP to induce the swallowing reflex and examined the involvement of the purinoreceptor P2×3 in this process. We observed that the topical application of exogenous ATP to the superior laryngeal nerve (SLN)-innervated swallowing-related regions dose-dependently facilitated the triggering of the swallowing reflex. P2×3 receptors were predominantly localised on nerve fibres in these regions. Immunoreactivity for P2×3 was observed in intraepithelial and subepithelial nerves, as well as nerves supplying taste-bud-like structures. In the nodose-petrosal-jugular ganglionic complex, P2×3 receptors were present on the cell bodies of approximately 40% of retrogradely traced SLN-afferent neurons. Among these P2×3-immunoreactive SLN-afferent neurons, approximately 59% were medium, 30% were small, and 11% were large. Prior topical application of a P2×3 antagonist in SLN-innervated, swallowing-related regions significantly reduced the number of ATP-induced swallowing reflexes. Furthermore, topical application of a P2×3 receptor agonist more selective than ATP facilitated reflex triggering in a dose-dependent manner. These findings suggest that exogenous ATP facilitates the triggering of the swallowing reflex through the activation of P2×3 receptors. This activation excites afferent neurons that supply peripheral swallowing-related regions, stimulating the swallowing central pattern generator to facilitate the reflex. The current findings suggest the therapeutic potential of ATP or P2×3 agonists for dysphagia treatment and provide valuable physiological insights into the involvement of purinergic signalling in triggering the swallowing reflex.