Abstract

(1) Background: Our previous studies revealed that orexin-A, an appetite-increasing peptide, suppressed reflex swallowing via the commissural part of the nucleus tractus solitarius (cNTS), and that glucagon-like peptide-1 (GLP-1), an appetite-reducing peptide, also suppressed reflex swallowing via the medial nucleus of the NTS (mNTS). In this study, we examined the mutual interaction between orexin-A and GLP-1 in reflex swallowing. (2) Methods: Sprague–Dawley rats under urethane–chloralose anesthesia were used. Swallowing was induced by electrical stimulation of the superior laryngeal nerve (SLN) and was identified by the electromyographic (EMG) signals obtained from the mylohyoid muscle. (3) Results: The injection of GLP-1 (20 pmol) into the mNTS reduced the swallowing frequency and extended the latency of the first swallow. These suppressive effects of GLP-1 were not observed after the fourth ventricular administration of orexin-A. After the injection of an orexin-1 receptor antagonist (SB334867) into the cNTS, an ineffective dose of GLP-1 (6 pmol) into the mNTS suppressed reflex swallowing. Similarly, the suppressive effects of orexin-A (1 nmol) were not observed after the injection of GLP-1 (6 pmol) into the mNTS. After the administration of a GLP-1 receptor antagonist (exendin-4(5-39)), an ineffective dose of orexin-A (0.3 nmol) suppressed reflex swallowing. (4) Conclusions: The presence of reciprocal inhibitory connections between GLP-1 receptive neurons and orexin-A receptive neurons in the NTS was strongly suggested.

Highlights

  • Swallowing is an early step in feeding behavior to propel food into the stomach, and is caused by simultaneous mastication and gastric accommodation

  • Our previous study and those of others demonstrated that the injection of a satiety peptide such as glucagon like peptide-1 (GLP-1), leptin, oxytocin, or nesfatin-1 into the rat dorsal medulla suppressed reflex swallowing induced by electrical stimulation of the superior laryngeal nerve (SLN), to appetite-enhancing peptides [7,8,9]

  • Our previous studies using the local administration of peptides, lesion of the area postrema (AP), and/or partial lesions of the nucleus tractus solitarius (NTS) clarified that orexin-A and GLP-1 act on the commissural part of the nucleus tractus solitarius (cNTS) and medial nucleus of the NTS (mNTS), respectively, to suppress reflex swallowing [6,9]

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Summary

Introduction

Swallowing is an early step in feeding behavior to propel food into the stomach, and is caused by simultaneous mastication and gastric accommodation. Our previous study and those of others demonstrated that the injection of a satiety peptide such as glucagon like peptide-1 (GLP-1), leptin, oxytocin, or nesfatin-1 into the rat dorsal medulla suppressed reflex swallowing induced by electrical stimulation of the SLN, to appetite-enhancing peptides [7,8,9]. Both appetite-increasing and -satiating substances suppress reflex swallowing. The role of this paradoxical response is thought to be helpful in keeping the ability of reflex swallowing constant even after meals [9]

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