Abstract

In pancreatic acini, cGMP can be increased by secretagogues such as cholecystokinin (CCK), cholinergic agents, and bombesin, whose actions on enzyme secretion are believed to be mediated by protein kinase C. However, the role of cGMP in acinar cell function has been unclear. A recent paper by Rogers et al. (Rogers, J., Hughes, R.G., and Matthews, E. K. (1988) J. Biol. Chem. 263, 3713-3719) reported that two analogues of cGMP, N2,O2-dibutyl guanosine 3':5'-monophosphate (Bt2cGMP) and 8-bromoguanosine 3':5'-monophosphate (8Br-cGMP), at concentrations in the nanomolar range, inhibited the stimulation of amylase secretion caused by CCK-8, bethanechol, bombesin, and 12-O-tetradecanoylphorbol-13-acetate (TPA). Rogers et al. also reported that sodium nitroprusside inhibited the stimulation of enzyme secretion caused by CCK-8 or TPA. These authors concluded that cGMP inhibits protein kinase C-mediated secretion in pancreatic acini. In the present study we attempted to confirm the findings of Rogers et al., We found, however, that Bt2cGMP inhibited CCK-8-stimulated amylase release only at concentrations of the nucleotide above 10 microM. Moreover, there was a close correlation between the ability of Bt2cGMP to inhibit CCK-8-stimulated amylase release and its ability to inhibit binding of 125I-CCK-8. Bt2cGMP, at concentrations as high as 3 mM, did not alter the stimulation of amylase release caused by carbachol, bombesin, TPA, or A23187. 8Br-cGMP, at concentrations up to 1 mM, did not inhibit the stimulation of amylase release caused by CCK-8 or TPA. At concentrations above 0.1 mM, 8Br-cGMP augmented the stimulation of amylase release caused by CCK-8, carbachol, bombesin, or TPA. Sodium nitroprusside, at a concentration that causes a 60-fold increase in cGMP, did not inhibit the stimulation of amylase release caused by CCK-8, carbachol, bombesin, or TPA. Our results do not confirm the findings of Rogers et al. and indicate that cGMP does not inhibit protein kinase C-mediated secretion in pancreatic acini.

Highlights

  • Howcally related secretogogues can be reproduced by derivatives of cAMP or by 8Br-cGMP.’ 8Br-cGMP produces the action of derivatives of cAMP by virtue of its ability to mimic the action of endogenous cAMP [2]

  • (1).Our findings reported in the present paper, do not confirm the previous results of Rogers et al [1] and indicate that cGMP does not inhibit protein kinase C-mediated enzyme secretion in rat pancreaticacini

  • We were unable to confirm this finding of Rogers et al [1].In agreement with previous results using rat as well as guinea pig pancreatic acini [6,7,8,9,10,11], we found that BhcGMP did not inhibit the action of CCK-8 until concentrationsof BtzcGMP of 10 p M and that this action was attributable to the ability of the cyclic nucleotide analogue to inhibit binding of CCK-8 toits receptor on pancreatic acini

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Summary

Introduction

At concentrations above0.1 mM, 8Br-cGMP augmented the stimulation of amylase release caused by CCK-8, carbachol, bombesin, or TPA. (1).Our findings reported in the present paper, do not confirm the previous results of Rogers et al [1] and indicate that cGMP does not inhibit protein kinase C-mediated enzyme secretion in rat pancreaticacini.

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