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. 1994 May 15;300(Pt 1):21–24. doi: 10.1042/bj3000021

Carbachol activates protein kinase C in dispersed gastric chief cells.

R D Raffaniello 1, J P Raufman 1
PMCID: PMC1138116  PMID: 8198535

Abstract

We used an 'in situ' kinase assay to examine agonist-induced protein kinase C. (PKC) activation in dispersed chief cells from guinea-pig stomach. Phorbol 12-myristate 13-acetate (PMA), a phorbol ester, and carbamoylcholine, a cholinergic agent, caused a 4- and 3-fold increase in pepsinogen secretion from dispersed chief cells respectively. Whereas PMA caused a rapid 3-fold increase in peptide kinase activity, carbachol caused a 15% increase in activity that was inhibited by the PKC inhibitor, CGP 41,251. Concentrations of carbamoylcholine and a Ca2+ ionophore that were sub-maximal for stimulation of pepsinogen secretion did not cause PKC activation. These results indicate that, in the absence of PKC activation, other mechanisms, most likely involving changes in cellular Ca2+, are sufficient to stimulate pepsinogen secretion. Nevertheless, carbamoylcholine stimulated maximal secretion of pepsinogen only at concentrations that also resulted in activation of PKC. Moreover, these data indicate that relatively small increases in PKC activity (5-10%) can stimulate pepsinogen secretion from dispersed chief cells.

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Selected References

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  1. Castagna M., Takai Y., Kaibuchi K., Sano K., Kikkawa U., Nishizuka Y. Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters. J Biol Chem. 1982 Jul 10;257(13):7847–7851. [PubMed] [Google Scholar]
  2. Chew C. S., Brown M. R. Histamine increases phosphorylation of 27- and 40-kDa parietal cell proteins. Am J Physiol. 1987 Dec;253(6 Pt 1):G823–G829. doi: 10.1152/ajpgi.1987.253.6.G823. [DOI] [PubMed] [Google Scholar]
  3. Heasley L. E., Johnson G. L. Detection of nerve growth factor and epidermal growth factor-regulated protein kinases in PC12 cells with synthetic peptide substrates. Mol Pharmacol. 1989 Mar;35(3):331–338. [PubMed] [Google Scholar]
  4. Heasley L. E., Johnson G. L. Regulation of protein kinase C by nerve growth factor, epidermal growth factor, and phorbol esters in PC12 pheochromocytoma cells. J Biol Chem. 1989 May 25;264(15):8646–8652. [PubMed] [Google Scholar]
  5. Kraft A. S., Anderson W. B. Phorbol esters increase the amount of Ca2+, phospholipid-dependent protein kinase associated with plasma membrane. Nature. 1983 Feb 17;301(5901):621–623. doi: 10.1038/301621a0. [DOI] [PubMed] [Google Scholar]
  6. Meyer T., Regenass U., Fabbro D., Alteri E., Rösel J., Müller M., Caravatti G., Matter A. A derivative of staurosporine (CGP 41 251) shows selectivity for protein kinase C inhibition and in vitro anti-proliferative as well as in vivo anti-tumor activity. Int J Cancer. 1989 May 15;43(5):851–856. doi: 10.1002/ijc.2910430519. [DOI] [PubMed] [Google Scholar]
  7. Nakano O., Sakamoto C., Nishisaki H., Konda Y., Matsuda K., Wada K., Nagao M., Matozaki T. Difference in effects of sodium fluoride and cholecystokinin on diacylglycerol accumulation and calcium increase in guinea pig gastric chief cells. Life Sci. 1990;47(7):647–654. doi: 10.1016/0024-3205(90)90577-e. [DOI] [PubMed] [Google Scholar]
  8. Raffaniello R. D., Raufman J. P. Cellular distribution of gastric chief cell protein kinase C activity: differential effects of diacylglycerol, phorbol esters, carbachol, and cholecystokinin. J Cell Biochem. 1992 Jan;48(1):107–113. doi: 10.1002/jcb.240480115. [DOI] [PubMed] [Google Scholar]
  9. Raffaniello R. D., Raufman J. P. Guanine nucleotides activate multiple signaling pathways in permeabilized gastric chief cells. Evidence for GTP gamma S-induced calcium-independent pepsinogen secretion. J Biol Chem. 1993 Apr 25;268(12):8491–8496. [PubMed] [Google Scholar]
  10. Raffaniello R. D., Raufman J. P. Pepsinogen secretion from streptolysin O-permeabilized chief cells from guinea pig stomach. Am J Physiol. 1992 Oct;263(4 Pt 1):G452–G459. doi: 10.1152/ajpgi.1992.263.4.G452. [DOI] [PubMed] [Google Scholar]
  11. Raufman J. P., Berger S., Cosowsky L., Straus E. Increases in cellular calcium concentration stimulate pepsinogen secretion from dispersed chief cells. Biochem Biophys Res Commun. 1986 May 29;137(1):281–285. doi: 10.1016/0006-291x(86)91207-6. [DOI] [PubMed] [Google Scholar]
  12. Raufman J. P. Gastric chief cells: receptors and signal-transduction mechanisms. Gastroenterology. 1992 Feb;102(2):699–710. doi: 10.1016/0016-5085(92)90124-h. [DOI] [PubMed] [Google Scholar]
  13. Sung C. K., Hootman S. R., Stuenkel E. L., Kuroiwa C., Williams J. A. Downregulation of protein kinase C in guinea pig pancreatic acini: effects on secretion. Am J Physiol. 1988 Feb;254(2 Pt 1):G242–G248. doi: 10.1152/ajpgi.1988.254.2.G242. [DOI] [PubMed] [Google Scholar]
  14. Terbush D. R., Holz R. W. Activation of protein kinase C is not required for exocytosis from bovine adrenal chromaffin cells. The effects of protein kinase C(19-31), Ca/CaM kinase II(291-317), and staurosporine. J Biol Chem. 1990 Dec 5;265(34):21179–21184. [PubMed] [Google Scholar]
  15. Tokumitsu H., Chijiwa T., Hagiwara M., Mizutani A., Terasawa M., Hidaka H. KN-62, 1-[N,O-bis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazi ne, a specific inhibitor of Ca2+/calmodulin-dependent protein kinase II. J Biol Chem. 1990 Mar 15;265(8):4315–4320. [PubMed] [Google Scholar]
  16. Tsunoda Y., Williams J. A., DelValle J. Secretagogue-induced Ca2+ oscillations in isolated canine gastric chief cells. Biochim Biophys Acta. 1991 Jan 31;1091(2):251–254. doi: 10.1016/0167-4889(91)90069-a. [DOI] [PubMed] [Google Scholar]
  17. Verme T. B., Velarde R. T., Cunningham R. M., Hootman S. R. Effects of staurosporine on protein kinase C and amylase secretion from pancreatic acini. Am J Physiol. 1989 Oct;257(4 Pt 1):G548–G553. doi: 10.1152/ajpgi.1989.257.4.G548. [DOI] [PubMed] [Google Scholar]

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