Are salivary glands cell lines in culture a good model for purinergic receptors in salivary glands?

A major obstacle in studying the physiological and biochemical processes of salivary secretion is the lack of a good ductal cell line model. HSY, an immortalised cell line originating from human parotid gland intercalated ducts, provides a possible model for purinergic mechanisms in ductal cells. Unlike the biphasic dose response to ATP of isolated submandibular ductal cells, the rise in [Ca²⁺](i) in HSY cells shows single Michaelis-Menten kinetics with an apparent K(a) of 0.8 μM. Pre-incubation with thapsigargin inhibited the ATP induced [Ca²⁺](i) rise. Both ATP (10 μM) and carbachol (100 μM) increased IP₃ production. Intercalated duct cells may differentiate into acinar or ductal cells in response to appropriate stimuli from extracellular matrix. We therefore attempted to induce a duct-like phenotype in the striated duct-derived HSY cells by growing them on microcarrier beads coated with type I collagen. In Ca-containing medium cells grown on all substrates showed similar responses to ATP. In contrast, in Ca- free medium, [Ca²⁺](i) rose only slightly in cells grown on beads relative to those on glass. This probably resulted from reduced IP₃ production. Carbachol also induced a much smaller increase in [Ca²⁺](i) and less IP₃ production in cells grown on Cytodex-3. The HSY response to purinergic stimuli by an increase in [Ca²⁺](i) and IP₃ means that they can be used to study the metabotropic purinergic pathway. The impairment in the HSY responses grown on Cytodex-3 can be used to probe phosposinositol signal transduction in salivary cells.