Spatial microenvironment defines Ca2+ entry and Ca2+ release in salivary gland cells

The difference of Ca2+ mobilization induced by muscarinic receptor activation between parotid acinar and duct cells was examined. Oxotremorine, a muscarinic-cholinergic agonist, induced intracellular Ca2+ release and extracellular Ca2+ entry through store-operated Ca2+ entry (SOC) and non-SOC channels in acinar cells, but it activated only Ca2+ entry from non-SOC channels in duct cells. RT-PCR experiments showed that both types of cells expressed the same muscarinic receptor, M3. Given that ATP activated the intracellular Ca2+ stores, the machinery for intracellular Ca2+ release was intact in the duct cells. By immunocytochemical experiments, IP3R2 colocalized with M3 receptors in the plasma membrane area of acinar cells; in duct cells, IP3R2 resided in the region on the opposite side of the M3 receptors. On the other hand, purinergic P2Y2 receptors were found in the apical area of duct cells where they colocalized with IP3R2. These results suggest that the expression of the IP3Rs near G-protein-coupled receptors is necessary for the activation of intracellular Ca2+ stores. Therefore, the microenvironment probably affects intracellular Ca2+ release and Ca2+ entry.