[Influence of ACh on the level of protein kinase C, intracellular free Ca(2+) and cyclic AMP/cyclic GMP of cultured human pituitary adenoma cells].
We found previously that ACh can significantly inhibit the proliferation of cultured human pituitary adenoma cells. In order to make a further investigation of the mechanism of the inhibitory effect of ACh on the proliferation of pituitary adenoma cells, we observed the levels of protein kinase C (PKC), [Ca(2+)](i) and cAMP/cGMP in cultured pituitary adenoma cells after treatment with ACh. The results demonstrate that (1) compared with control, PMA, a PKC activator, increased the activity of cytoplasm, membrane and total PKC in human pituitary adenoma cells. However, after a 15-min treatment with ACh (10 micromol/L), a significant reduction of the activity of cytoplasm, membrane and total PKC in human pituitary adenoma cells was observed, and the reduction effect could be blocked by atropine. (2) The level of [Ca(2+)](i) of single adenoma cells was found to decrease immediately on the addition of ACh (10 micromol/L), which could also be blocked by atropine. (3) ACh increased the amount of cAMP in the cytoplasm of human pituitary adenoma cells, but had no effect on that of cGMP. These data provide an important clue to explore the molecular mechanisms of the inhibitory effect of ACh on the proliferation of pituitary adenoma cells, and suggest that the modulating effect of ACh on the proliferation of pituitary adenoma cells results from the interactions of several cellular signaling pathways.
Chi
Su-Min
SM
Department of Physiology, the Fourth Military Medical University, Xi'an, PR China. chisumin@yahoo.com
Li
Cheng-Xin
CX
Liu
Ya-Li
YL
Zhu
Yun-Long
YL
Gu
Jian-Wen
JW
D000109:Acetylcholine / Q000502:physiology*; D000236:Adenoma / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism; D006801:Humans; D010911:Pituitary Neoplasms / Q000378:metabolism* / Q000473:pathology; D011493:Protein Kinase C / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014407:Tumor Cells, Cultured
D000242:Cyclic AMP; D011493:Protein Kinase C; D006152:Cyclic GMP; D000109:Acetylcholine; D002118:Calcium