Trp1‐dependent enhancement of salivary gland fluid secretion: role of store‐operated calcium entry

ABSTRACT This study examined the involvement of store‐operated Ca2+ entry in agonist‐stimulation of salivary gland fluid secretion. A recombinant adenovirus (AdCMV‐hTrp1) encoding the store‐operated Ca2+ channel protein, human transient receptor potential 1 (hTrp1), was used to direct expression of HA (hemaglutinin )‐tagged hTrp1 in vivo in rat submandibular glands (SMG) and in vitro in the human submandibular gland cell line (HSG). Studies with HSG cells demonstrated that AdCMV‐hTrp1 was successful in directing the expression of functional hTrp1 and that it did not affect early Ca2+ signaling events. AdCMV‐hTrp1‐infected SMG displayed an increase in the level of Trp1 and a fivefold increase in pilocarpine‐stimulated fluid secretion, compared with glands infected with a control adenovirus encoding luciferase (AdCMV‐Luc). The expressed hTrp1 demonstrated polarized localization in the basolateral plasma membrane region of SMG acinar cells and was co‐immunoprecipitated with IP3Rs. Further, acinar cells isolated from AdCMV‐hTrp1‐infected glands demonstrated a significant increase in carbachol‐ and Tg‐stimulated Ca2+ entry compared with cells isolated from AdCMV‐Luc‐infected glands. We conclude that in vivo expression of Trp1 in SMG induces an enhancement of agonist‐stimulated fluid secretion via increasing store‐operated Ca2+ entry into acinar cells. These data suggest that store‐operated Ca2+ entry has a role in agonist‐stimulated fluid secretion from salivary glands.