title: Mechanisms Underlying Activation of α₁-Adrenergic Receptor-Induced Trafficking of AQP5 in Rat Parotid Acinar Cells under Isotonic or Hypotonic Conditions.
abstract: Defective cellular trafficking of aquaporin-5 (AQP5) to the apical plasma membrane (APM) in salivary glands is associated with the loss of salivary fluid secretion. To examine mechanisms of α₁-adrenoceptor (AR)-induced trafficking of AQP5, immunoconfocal microscopy and Western blot analysis were used to analyze AQP5 localization in parotid tissues stimulated with phenylephrine under different osmolality. Phenylephrine-induced trafficking of AQP5 to the APM and lateral plasma membrane (LPM) was mediated via the α1A-AR subtype, but not the α1B- and α1D-AR subtypes. Phenylephrine-induced trafficking of AQP5 was inhibited by ODQ and KT5823, inhibitors of nitric oxide (NO)-stimulated guanylcyclase (GC) and protein kinase (PK) G, respectively, indicating the involvement of the NO/ soluble (c) GC/PKG signaling pathway. Under isotonic conditions, phenylephrine-induced trafficking was inhibited by La(3+), implying the participation of store-operated Ca(2+) channel. Under hypotonic conditions, phenylephrine-induced trafficking of AQP5 to the APM was higher than that under isotonic conditions. Under non-stimulated conditions, hypotonicity-induced trafficking of AQP5 to the APM was inhibited by ruthenium red and La(3+), suggesting the involvement of extracellular Ca(2+) entry. Thus, α1A-AR activation induced the trafficking of AQP5 to the APM and LPM via the Ca(2+)/ cyclic guanosine monophosphate (cGMP)/PKG signaling pathway, which is associated with store-operated Ca(2+) entry.
authors.affiliation: Department of Medical Pharmacology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima 770-8504, Japan. aneta.bragiel@gmail.com.
authors.forename: Aneta M
authors.initials: AM
authors.lastname: Bragiel
authors.affiliation: Department of Medical Pharmacology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima 770-8504, Japan. wangdic@126.com.
authors.forename: Di
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Medical Pharmacology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima 770-8504, Japan. c301251017@tokushima-u.ac.jp.
authors.forename: Tomasz D
authors.initials: TD
authors.lastname: Pieczonka
authors.affiliation: Support Center for Advanced Medical Sciences, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima 770-8504, Japan. masa@md.tokushima-u.ac.jp.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Shono
authors.affiliation: Department of Medical Pharmacology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima 770-8504, Japan. yisikawa@tokushima-u.ac.jp.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Ishikawa
mesh_terms: D061354:Acinar Cells / Q000187:drug effects / Q000378:metabolism*; D058646:Adrenergic alpha-1 Receptor Agonists / Q000494:pharmacology; D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D051402:Aquaporin 5 / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005677:G(M1) Ganglioside / Q000378:metabolism; D007038:Hypotonic Solutions / Q000494:pharmacology; D007150:Immunohistochemistry; D007552:Isotonic Solutions / Q000494:pharmacology; D008297:Male; D010306:Parotid Gland / Q000166:cytology*; D010646:Phentolamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D051402:Aquaporin 5; D007038:Hypotonic Solutions; D007552:Isotonic Solutions; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; D005677:G(M1) Ganglioside; D010646:Phentolamine
keywords: aquaporin-5; calcium; hypotonicity; protein G kinase; α1A-adrenoceptor; α1B-adrenoceptor; α1D-adrenoceptor