title: Functional differences in the acinar cells of the murine major salivary glands.
abstract: In humans, approximately 90% of saliva is secreted by the 3 major salivary glands: the parotid (PG), the submandibular (SMG), and the sublingual glands (SLG). Even though it is known that all 3 major salivary glands secrete saliva by a Cl(-)-dependent mechanism, salivary secretion rates differ greatly among these glands. The goal of this study was to gain insight into the properties of the ion-transporting pathways in acinar cells that might account for the differences among the major salivary glands. Pilocarpine-induced saliva was simultaneously collected in vivo from the 3 major salivary glands of mice. When normalized by gland weight, the amount of saliva secreted by the PG was more than 2-fold larger than that obtained from the SMG and SLG. At the cellular level, carbachol induced an increase in the intracellular [Ca(2+)] that was more than 2-fold larger in PG and SMG than in SLG acinar cells. Carbachol-stimulated Cl(-) efflux and the protein levels of the Ca(2+)-activated Cl(-) channel TMEM16A, the major apical Cl(-) efflux pathway in salivary acinar cells, were significantly greater in PG compared with SMG and SLG. In addition, we evaluated the transporter activity of the Na(+)-K(+)-2Cl(-) cotransporters (NKCC1) and anion exchangers (AE), the 2 primary basolateral Cl(-) uptake mechanisms in acinar cells. The SMG NKCC1 activity was about twice that of the PG and more than 12-fold greater than that of the SLG. AE activity was similar in PG and SLG, and both PG and SLG AE activity was about 2-fold larger than that of SMG. In summary, the salivation kinetics of the 3 major glands are distinct, and these differences can be explained by the unique functional properties of each gland related to Cl(-) movement, including the transporter activities of the Cl(-) uptake and efflux pathways, and intracellular Ca(2+) mobilization.
authors: Secretory Mechanisms and Dysfunction Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA Department of Oral Reconstruction and Rehabilitation, Kyushu Dental University, Kitakyushu, Fukuoka, Japan.
authors: Y
authors: Y
authors: Kondo
authors: Department of Oral Reconstruction and Rehabilitation, Kyushu Dental University, Kitakyushu, Fukuoka, Japan.
authors: T
authors: T
authors: Nakamoto
authors: Secretory Mechanisms and Dysfunction Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
authors: Y
authors: Y
authors: Jaramillo
authors: Secretory Mechanisms and Dysfunction Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
authors: S
authors: S
authors: Choi
authors: Secretory Mechanisms and Dysfunction Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
authors: M A
authors: MA
authors: Catalan
authors: Secretory Mechanisms and Dysfunction Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA james.melvin@nih.gov.
authors: J E
authors: JE
authors: Melvin
mesh_terms: D000818:Animals; D000075369:Anoctamin-1; D017920:Antiporters / Q000378:metabolism; D001639:Bicarbonates / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D018118:Chloride Channels / Q000187:drug effects; D002713:Chlorine / Q000378:metabolism; D017136:Ion Transport / Q000502:physiology; D051379:Mice; D018721:Muscarinic Agonists / Q000494:pharmacology; D009929:Organ Size; D010306:Parotid Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010862:Pilocarpine / Q000494:pharmacology; D012463:Saliva / Q000187:drug effects / Q000378:metabolism; D018987:Salivary Ducts / Q000166:cytology / Q000378:metabolism; D012472:Salivation / Q000187:drug effects / Q000502:physiology; D064506:Solute Carrier Family 12, Member 2 / Q000378:metabolism; D013361:Sublingual Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013363:Submandibular Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: C531181:ANO1 protein, mouse; D000075369:Anoctamin-1; D017920:Antiporters; D001639:Bicarbonates; D018118:Chloride Channels; D018721:Muscarinic Agonists; C578878:Slc12a2 protein, mouse; D064506:Solute Carrier Family 12, Member 2; D010862:Pilocarpine; D002713:Chlorine; D002217:Carbachol
keywords: Na-K-Cl transporter; calcium signaling; chloride channel; epithelia; physiology; salivary physiology