Extracellular nucleotides have been implicated in the regulation of secretory function through the activation of P2 receptors in the epithelial tissues, including tracheal epithelial cells (TECs). In this study, experiments were conducted to characterize the P2 receptor subtype on canine TECs responsible for stimulating inositol phosphate (Ins P x) accumulation and Ca2+ mobilization using a range of nucleotides. The nucleotides ATP and UTP caused a concentration-dependent increase in [3H]Ins P xaccumulation and Ca2+ mobilization with comparable kinetics and similar potency. The selective agonists for P1, P2X, and P2Y1 receptors, N 6-cyclopentyladenosine and AMP, α,β-methylene-ATP and β,γ-methylene-ATP, and 2-methylthio-ATP, respectively, had little effect on these responses. Stimulation of TECs with maximally effective concentrations of ATP and UTP showed no additive effect on [3H]Ins P xaccumulation. The response of a maximally effective concentration of either ATP or UTP was additive to the response evoked by bradykinin. Furthermore, ATP and UTP induced a cross-desensitization in [3H]Ins P x accumulation and Ca2+ mobilization. These results suggest that ATP and UTP directly stimulate phospholipase C-mediated [3H]Ins P x accumulation and Ca2+ mobilization in canine TECs. P2Y2receptors may be predominantly mediating [3H]Ins P x accumulation, and, subsequently, inositol 1,4,5-trisphosphate-induced Ca2+mobilization may function as the transducing mechanism for ATP-modulated secretory function of tracheal epithelium.
Effects of transformation with the v-src oncogene on inositol phosphate metabolism in rat-1 fibroblasts. D-myo-inositol 1,4,5,6-tetrakisphosphate is increased in v-src-transformed rat-1 fibroblasts and can be synthesized from D-myo-inositol 1,3,4-trisphosphate in cytosolic extracts
