title: Pituitary adenylate cyclase-activating polypeptide enhances saliva secretion via direct binding to PACAP receptors of major salivary glands in mice.
abstract: Xerostomia, or dry mouth, is a common syndrome that is generally treated with artificial saliva; however, no other effective methods have yet been established. Saliva secretion is mainly under the control of the autonomic nervous system. Pituitary adenylate cyclase-activating polypeptide (PACAP) is recognized as a multifunctional neuropeptide in various organs. In this study, we examined the effect of PACAP on saliva secretion, and detected the distribution of the PACAP type 1 receptor (PAC1R) in major salivary glands, including the parotid, submandibular, and sublingual glands, in 9-week-old male C57BL/6 mice. Intranasal administration of PACAP 38 increased the amount of saliva secreted, which was not inhibited by atropine pretreatment. Immunohistochemical analysis showed that PAC1R was distributed in the three major salivary glands. In the parotid and sublingual glands, PAC1R was detected in striated duct cells, whereas in the submandibular gland, a strong PAC1R immunoreaction was detected in tall columnar epithelial cells in the granular ducts (i.e., pillar cells), as well as in some striated duct cells. PACAP significantly increased the concentration of epidermal growth factor in saliva. These results suggest that PACAP directly regulates saliva secretion by controlling the absorption activity in the ducts, and that pillar cells regulate the function of granular epithelial cells in the granular duct, such as the secretion of growth factors into the saliva. Collectively, these results suggest the possibility of PACAP as a new effective treatment of xerostomia. Anat Rec, 299:1293-1299, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Oral Anatomy and Developmental Biology, Showa University School of Dentistry, Shinagawa-Ku, Tokyo, Japan.|Division of Oral Surgery, Yokohama General Hospital, Aoba-Ku, Yokohama, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Matoba
authors.affiliation: Department of Oral Anatomy and Developmental Biology, Showa University School of Dentistry, Shinagawa-Ku, Tokyo, Japan.|Geriatrics Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA.
authors.forename: Naoko
authors.initials: N
authors.lastname: Nonaka
authors.affiliation: Department of Oral Anatomy and Developmental Biology, Showa University School of Dentistry, Shinagawa-Ku, Tokyo, Japan.
authors.forename: Yoshitoki
authors.initials: Y
authors.lastname: Takagi
authors.affiliation: Department of Oral Anatomy and Developmental Biology, Showa University School of Dentistry, Shinagawa-Ku, Tokyo, Japan.|Division of Oral Surgery, Yokohama General Hospital, Aoba-Ku, Yokohama, Japan.
authors.forename: Eisaku
authors.initials: E
authors.lastname: Imamura
authors.affiliation: Department of Oral Anatomy and Developmental Biology, Showa University School of Dentistry, Shinagawa-Ku, Tokyo, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Narukawa
authors.affiliation: Laboratory of Regulatory Biology, Graduate School of Science and Engineering, University of Toyama, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Nakamachi
authors.affiliation: Global Research Center for Innovative Life Science, Hoshi University, Shinagawa-Ku, Tokyo, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Shioda
authors.affiliation: Geriatrics Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA.
authors.forename: William A
authors.initials: WA
authors.lastname: Banks
authors.affiliation: Department of Oral Anatomy and Developmental Biology, Showa University School of Dentistry, Shinagawa-Ku, Tokyo, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D004815:Epidermal Growth Factor / Q000032:analysis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000008:administration & dosage*; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide / Q000378:metabolism*; D012463:Saliva / Q000737:chemistry / Q000378:metabolism*; D012469:Salivary Glands / Q000187:drug effects* / Q000378:metabolism
chemical_list: D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D004815:Epidermal Growth Factor
keywords: PAC1R; PACAP; pillar cell; salivary gland