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 La3+, implying the participation of store-operated Ca2+ 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 La3+, suggesting the involvement of extracellular Ca2+ entry. Thus, α1A-AR activation induced the trafficking of AQP5 to the APM and LPM via the Ca2+/ cyclic guanosine monophosphate (cGMP)/PKG signaling pathway, which is associated with store-operated Ca2+ entry.
Highlights
IntroductionActivation of M1- and M3-muscarinic acetylcholine receptors (mAChRs) and α1-adrenoceptors (ARs) induce an increase in the cytosolic concentration of calcium ([Ca2+]i) and stimulate salivary fluid secretion [2]
Salivary secretion is regulated by both sympathetic and parasympathetic nerves [1]
These data are highly similar to the time-dependent increase of AQP5 levels in the apical plasma membrane (APM) of rat parotid tissues induced by phenylephrine
Summary
Activation of M1- and M3-muscarinic acetylcholine receptors (mAChRs) and α1-adrenoceptors (ARs) induce an increase in the cytosolic concentration of calcium ([Ca2+]i) and stimulate salivary fluid secretion [2]. In in vitro studies using rat parotid gland slices, the interactions of acetylcholine (ACh) and epinephrine with M3-mAChRs [8] and α1-ARs [9], respectively, induce a rapid trafficking of AQP5 to the apical plasma membrane (APM) via the enhanced [Ca2+]i. The hypotonic conditions activate the transient receptor potential (TRPV) 4 and induce the trafficking of AQP5 to the APM in human salivary gland cells [28] and reduction of AQP5 in lung epithelial cells [29]. To clarify the relationship between α1-AR activation, osmolality and TRPV4, the mechanisms underlying α1-AR induced the trafficking of AQP5 were investigated under different osmolality in rat parotid glands
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