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

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 IP(3)Rs. 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.