title: Human salivary gland cells express bradykinin receptors that modulate the expression of proinflammatory cytokines.
abstract: Bradykinin is an important peptide modulator that affects the function of neurons and immune cells. However, there is no evidence of the bradykinin receptors and their functions in human salivary glands. Here we have identified and characterized bradykinin receptors on human submandibular gland cells. Both bradykinin B1 and B2 receptors are expressed on human submandibular gland cells, A253 cells, and HSG cells. Bradykinin increased the intracellular Ca2+concentration ([Ca2+]i) in a concentration-dependent manner. Interestingly, a specific agonist of the B1 receptor did not have any effect on [Ca2+]iin HSG cells, whereas specific agonists of the B2 receptor had a Ca2+mobilizing effect. Furthermore, application of the B1 receptor antagonist, R715, did not alter the bradykinin-mediated increase in cytosolic Ca2+, whereas the B2 receptor antagonist, HOE140, showed a strong inhibitory effect, which implies that bradykinin B2 receptors are functional in modulating the concentration of cytosolic Ca2+. Bradykinin did not affect a carbachol-induced rise of [Ca2+]iand did not modulate translocation of aquaporin-5. However, bradykinin did promote the expression of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), implying the role of bradykinin in salivary gland inflammation. These data suggest that bradykinin receptors are involved in Ca2+signaling in human submandibular gland cells and serve a unique role, which is separate from that of other salivary gland G protein-coupled receptors.
authors.affiliation: Department of Physiology, Dental Research Institute, Seoul National University School of Dentistry, Seoul, Korea.
authors.forename: Keimin
authors.initials: K
authors.lastname: Lee
authors.affiliation: Department of Physiology, Dental Research Institute, Seoul National University School of Dentistry, Seoul, Korea.
authors.forename: Yoon-Jung
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Physiology, Dental Research Institute, Seoul National University School of Dentistry, Seoul, Korea.
authors.forename: La-Mee
authors.initials: LM
authors.lastname: Choi
authors.affiliation: Department of Physiology, Dental Research Institute, Seoul National University School of Dentistry, Seoul, Korea.
authors.forename: Seulki
authors.initials: S
authors.lastname: Choi
authors.affiliation: Department of Oral Biochemistry, Dental Research Institute, Seoul National University School of Dentistry, Seoul, Korea.
authors.forename: Hyun
authors.initials: H
authors.lastname: Nam
authors.affiliation: Department of Physiology, Dental Research Institute, Seoul National University School of Dentistry, Seoul, Korea.
authors.forename: Hui-Yeon
authors.initials: HY
authors.lastname: Ko
authors.affiliation: Department of Physiology, Dental Research Institute, Seoul National University School of Dentistry, Seoul, Korea.
authors.forename: Gehoon
authors.initials: G
authors.lastname: Chung
authors.affiliation: Department of Oral and Maxillofacial Surgery, Dental Research Institute, Seoul National University School of Dentistry, Seoul, Korea.
authors.forename: Jong-Ho
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Physiology, Kangwon National University School of Medicine, Chuncheon, Korea.
authors.forename: Su-Hyun
authors.initials: SH
authors.lastname: Jo
authors.affiliation: Department of Oral Biochemistry, Dental Research Institute, Seoul National University School of Dentistry, Seoul, Korea.
authors.forename: Gene
authors.initials: G
authors.lastname: Lee
authors.affiliation: Department of Physiology, Dental Research Institute, Seoul National University School of Dentistry, Seoul, Korea.
authors.forename: Se-Young
authors.initials: SY
authors.lastname: Choi
authors.affiliation: Department of Physiology, Dental Research Institute, Seoul National University School of Dentistry, Seoul, Korea.
authors.forename: Kyungpyo
authors.initials: K
authors.lastname: Park
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051402:Aquaporin 5 / Q000378:metabolism; D015153:Blotting, Western; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D018002:Receptors, Bradykinin / Q000378:metabolism*; D012469:Salivary Glands / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C496036:AQP5 protein, human; D051402:Aquaporin 5; D016207:Cytokines; C120984:R 715; D018002:Receptors, Bradykinin; D014409:Tumor Necrosis Factor-alpha; C065679:icatibant; D002217:Carbachol; D000242:Cyclic AMP; D001920:Bradykinin; D002118:Calcium
keywords: aquaporin; bradykinin; cytokine; human submandibular gland; intracellular calcium