Cevimeline enhances the excitability of rat superior salivatory neurons.
Cevimeline, a therapeutic drug for xerostomia, is an agonist of muscarinic acetylcholine receptors (mAChRs), and directly stimulates the peripheral mAChRs of the salivary glands. Since cevimeline is distributed in the brain after its oral administration, it is possible that it affects the central nervous system. However, it is unknown how cevimeline affects the superior salivatory (SS) neurons, which control submandibular salivation. In the present study, we examined the effects of cevimeline on the SS neurons using the whole-cell patch-clamp technique in brain slices. In Wistar rats (6-10 days), the SS neurons were retrogradely labeled by Texas Red applied to the chorda-lingual nerve. Two days after injection, whole-cell recordings were obtained from the labeled cells, and miniature excitatory postsynaptic currents (mEPSCs) were examined. Cevimeline induced the inward currents dose-dependently and increased the frequency of mEPSCs. Therefore, it is suggested that cevimeline enhances the excitability via post- and presynaptic muscarinic receptors in the rat SS neurons. In conclusion, cevimeline may enhance the excitability of the SS neurons.
Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University, Okayama, Japan.
Hirotaka
H
Ueda
Yoshihiro
Y
Mitoh
Hiroyuki
H
Ichikawa
Motoi
M
Kobashi
Takashi
T
Yamashiro
Ryuji
R
Matsuo
D000818:Animals; D004305:Dose-Response Relationship, Drug; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology; D008526:Medulla Oblongata / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D023421:Models, Animal; D018721:Muscarinic Agonists / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D011812:Quinuclidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000502:physiology; D012472:Salivation / Q000502:physiology; D013363:Submandibular Gland / Q000294:innervation / Q000502:physiology; D013876:Thiophenes / Q000494:pharmacology*
D018721:Muscarinic Agonists; D011812:Quinuclidines; D011976:Receptors, Muscarinic; D013876:Thiophenes; C059240:cevimeline