Akihiko TANIMURA

Akihiro NEZU

MST. Tahmina AKTER

MST. Tahmina, AKTER

38799

Akihiro, NEZU

38800

Akihiko, TANIMURA

38801

Health Sciences University of Hokkaido Academic Repository / 北海道医療大学学術リポジトリ

北海道医療大学学術リポジトリRecent findings on the therapeutic effects ofpilocarpine on dry mouth著者 MST. Tahmina AKTER, Akihiro NEZU, AkihikoTANIMURAjournal orpublication titleThe Dental Journal of Health SciencesUniversity of Hokkaidovolume 41number 1page range 27-28year 2022-06-30URL http://id.nii.ac.jp/1145/00065106/［最近のトピックス］Recent findings on the therapeutic effects of pilocarpine on dry mouthMST. Tahmina AKTER, Akihiro NEZU, Akihiko TANIMURADivision of Pharmacology, Department of Oral Biology, School of Dentistry, Health Sciences University of HokkaidoPilocarpine, used as a treatment for dry mouth, is a partialagonist of muscarinic acetylcholine receptors ( mAChRs ) ,and induces salivation through a rise in the intracellular Ca2+concentration ([Ca2+]i) by activating mAChRs in salivary aci-nar cells. In rodents, a 0.1~10 mg (mg/kg, intraperitonealadministration) dose of pilocarpine induces salivary secre-tion. Such a dose is similar to a 3~100 µM (0.7~35 µg/mL)concentration which increases the [Ca2+]i in isolated salivarygland cells (Fig 1A, Nezu et al., 2015).Clinically, pilocarpine ( Salagen® tablets ) is prescribedorally in a dosage of 5 mg/tablet. According to the instruc-tions provided with Salagen® tablets, this dose of pilocarpinedoes not cause salivation after oral administration, but im-proves salivation after continuous administration of pilo-carpine for more than 12 weeks. The maximum blood con-centration ( Cmax ) of a single oral dose of pilocarpine isaround 30 ng/mL. This concentration is estimated to be ap-proximately 0.1 µM, less than one−thirtieth of the concentra-tion that increases [Ca2+]i in in vitro experiments. This sug-gests that mechanisms other than the mAChR−mediated Ca2+responses may be involved in the improvement of salivationby Salagen® tablets (Fig. 1A). Recently, Minagi−Ono et al.(2018) reported what may provide a possible answer to themechanism for improving salivation by Salagen® tablets.At Osaka University Dental Hospital, pilocarpine is usedfor patients with Sjögren’s syndrome (SS). The hospital pre-scribes pilocarpine at about half of the usual dose to reduceside effects such as nausea, and examined salivary secretionsby the Saxon test and the visual analog scale after the treat-ment for more than 12 weeks. The results showed signifi-cant improvements in these evaluations, indicating that con-tinuous administration of pilocarpine improves the salivaryfunction in SS patients, even at low doses (Minagi−Ono etal., 2018).Next, Minagi−Ono et al. analyzed salivary secretion, cellmorphology, protein, and gene expression after a continuousoral administration of the low−dose of pilocarpine in wildtype and SS model mice. Two−weeks of pilocarpine (1 mg/10 mL/kg, orally, Twice daily) administration significantlyincreased salivary secretion in these mice. This study alsoshowed a significant increase in the protein and gene expres-sion of M3 mAChR in the salivary glands of the pilocarpine−treated mice (Fig. 1B), suggesting that the increase in theexpression level of M3 mAChR may contribute to the im-provement of salivary secretion (Minagi−Ono et al., 2018).Pilocarpine has been thought to improve salivation via theCa2+−dependent fluid secretion in the treatment of dry mouthby Salagen® Tablets. This study provides new insight intothe mechanism by which pilocarpine improves dry mouth :the up−regulation of the expression of M3 mAChR in sali-vary gland cells (Fig. 1B). The mechanism for the increasein the expression of M3 mAChR by pilocarpine remains un-clear. Elucidation of this mechanism may lead to the devel-opment of a new treatment for dry mouth.ReferencesMinagi−Ono H, Ikai K, Araie T, Sakai M & Sakai T.Benefits of long−term pilocarpine due to increased mus-carinic acetylcholine receptor 3 in salivary glands. Bio-chem Biophys Res Commun, 503 (2), 1098−1102, 2018.Nezu A, Morita T, Tojyo Y, Nagai T & Tanimura A. Par-tial agonistic effects of pilocarpine on Ca2+ responses andsalivary secretion in the submandibular glands of live ani-mals. Exp Physiol, 100.6, 640−651, 2015.27北海道医療大学歯学雑誌 41 令和4年（27）第４１巻１号　　　４Ｃ１５０　１Ｃ１３３／本文　※３１‐１から組体裁変更　ＯＴＦ／０２７～０２８　トピックス　Ｔａｈｍｉｎ  2022.08.03 08.46.09  Page 27 Figure 1 : Mechanism of the therapeutic effect of pilocarpine with dry mouth.A) Mechanisms of pilocarpine−induced salivary fluid secretion through the activation of mAChR in in vitro experi-ments. B) Mechanisms of continuous administration of pilocarpine in clinical and in vivo experiments. ACh : acetyl-choline.28 北海道医療大学歯学雑誌 41 令和4年（28）第４１巻１号　　　４Ｃ１５０　１Ｃ１３３／本文　※３１‐１から組体裁変更　ＯＴＦ／０２７～０２８　トピックス　Ｔａｈｍｉｎ  2022.08.03 08.46.09  Page 28 

Recent findings on the therapeutic effects of pilocarpine on dry mouth

https://hsuh.repo.nii.ac.jp/?action=repository_action_common_download&item_id=11339&item_no=1&attribute_id=22&file_no=1

Recent findings on the therapeutic effects of pilocarpine on dry mouth

Abstract

Similar works

Full text

Available Versions

Health Sciences University of Hokkaido Academic Repository / 北海道医療大学学術リポジトリ