Effects of forksolin, dibutyryl cAMP and H89 on Ca2+ mobilization in submandibular salivary cells of newborn rats.

The effects of substances which affect cAMP or the cAMP-dependent protein kinase (PKA) on the inositol 1,4,5-trisphosphate (IP3) and Ca2+ responses to acetylcholine or thapsigargin were investigated in submandibular gland cells of newborn rats. Exposure to forskolin, dibutyryl cAMP or the PKA inhibitor H89 did not affect the formation of IP3 or the release of Ca2+ from intracellular stores elicited by acetylcholine. However, the thapsigargin-induced Ca2+ release was reduced by dibutyryl cAMP and enhanced by H89 in immature cells. Ca2+ influx activated by acetylcholine and thapsigargin was additive in immature cells but not in mature cells, suggesting the presence of a separate Ca2+ entry pathway in immature cells. Moreover, the acetylcholine-stimulated Ca2+ influx was significantly potentiated by forskolin and dibutyrylcAMP, but not by H89 in immature cells. In contrast, the thapsigargin-activated Ca2+ influx was dramatically enhanced by H89, but not by forskolin and dibutyrylcAMP in these cells. This modulation of Ca2+ mobilization by the test substances is different from that observed in mature submandibular cells in which forskolin, dibutyrylcAMP and H89 affected both IP3 formation and Ca2+ release in response to acetylcholine. Therefore, these results suggest differences in the interaction between the cAMP-PKA and the phosphoinositide-Ca2+ signalling pathways of mature and immature salivary cells. The modulation of Ca2+ influx by the cAMP-PKA pathway in immature cells is likely to play a part in the maturation of salivary cells.