Regulation of zymogen granule exocytosis by Ca2+, cAMP, and PKC in pancreatic acinar cells.
The effect of cAMP and PKC on zymogen granule exocytosis was investigated by simultaneously measuring cytosolic Ca2+ concentration ([Ca2+]c) and individual zymogen granule exocytosis in isolated mouse pancreatic acini. When acinar cells were stimulated with acetylcholine (ACh, 10 microM), exocytic events were detected through granule-attached apical membranes with [Ca2+]c rise. Application of secretin, forskolin (an adenylate cyclase activator), or PMA (a PKC activator) alone did not elicit any [Ca2+]c rise or zymogen granule exocytosis, but co-stimulation with ACh led to exocytosis in that the total number of secreted granules increased markedly without a significant difference in [Ca2+]c rises. When we evoked exocytosis by [Ca2+]c ramps, pretreatment with forskolin or PMA elicited exocytosis at lower [Ca2+]c levels. These results indicate that PKC or cAMP alone could not directly elicit zymogen granule exocytosis, but that they increase the total releasable pool by rendering zymogen granules more sensitive to Ca2+.
Lee
Misun
M
Department of Physiology, Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, 300 Chunchun-dong Jangan-ku, Suwon 440-746, Republic of Korea.
Chung
Sungkwon
S
Uhm
Dae Yong
DY
Park
Myoung Kyu
MK
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D005089:Exocytosis / Q000502:physiology*; D051379:Mice; D010179:Pancreas / Q000166:cytology / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D022142:Secretory Vesicles / Q000502:physiology* / Q000648:ultrastructure
D000242:Cyclic AMP; D011493:Protein Kinase C; D002118:Calcium