Effects of forskolin, 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 k inase (PKA) on the inositol 1,4,5-trisphosphate (IP3) and Ca2+ responses to acetylcholine or thapsigargin were investigated in submandibular gland cel ls of newborn rats. Exposure to forskolin, dibutyryl cAMP or the PKA inhibi tor H89 did not affect the formation of IP3 or the release of Ca2+ from int racellular stores elicited by acetylcholine. However, the thapsigargin-indu ced Ca2+ release was reduced by dibutyryl cAMP and enhanced by H89 in immat ure cells. Ca2+ influx activated by acetylcholine and thapsigargin was addi tive in immature cells but not in mature cells, suggesting the presence of a separate Ca2+ entry pathway in immature cells. Moreover, the acetylcholin e-stimulated Ca2+ influx was significantly potentiated by forskolin and dib utyrylcAMP, but not by H89 in immature cells. In contrast, the thapsigargin -activated Ca2+ influx was dramatically enhanced by H89, but not by forskol in and dibutyrylcAMP in these cells. This modulation of Ca2+ mobilization b y the test substances is different from that observed in mature submandibul ar cells in which forskolin, dibutyrylcAMP and H89 affected both IP3 format ion and Ca2+ release in response to acetylcholine. Therefore, these results suggest differences in the interaction between the cAMP-PKA and the phosph oinositide-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. (C) 1999 Elsevie r Science Ltd. All rights reserved.