Inhibitory effect of calcium-binding protein regucalcin on protein kinase C activity in rat liver cytosol

In previous studies we demonstrated that parietal cell stimulation with gastrin and carbamoylcholine (carbachol) is accompanied by increased turnover of membrane inositol phospholipids. We conducted the present studies to examine whether membrane-associated protein kinase C activity is enhanced as a consequence of these events and to explore the role of this enzyme in regulating parietal cell function. We observed that carbachol and gastrin dose dependently increased membrane-associated protein kinase C activity while histamine did not. Furthermore, compounds such as phorbol esters and diacylglycerol, which are known to be direct stimulants of protein kinase C activity, also stimulated parietal cell aminopyrine uptake. In contrast, the phorbol ester 12-O-tetradecanoylphorbol-13-acetate and the synthetic diacylglycerol 1-oleoyl-2-acetyl-sn-glycerol inhibited both aminopyrine uptake and membrane inositol phospholipid turnover in parietal cells induced by carbachol and gastrin. The inhibitory effect appeared to result from reduction in the quantity of muscarinic and gastrin receptors without alterations in their specific affinities. These data suggest that protein kinase C mediates stimulation of parietal cells by gastrin and carbachol but also activates an autoregulatory mechanism via downregulation of muscarinic and gastrin receptors.

Download Full-text

Caerulein-induced NF-κB/Rel activation requires both Ca2+ and protein kinase C as messengers

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1999.277.3.g678 ◽

1999 ◽

Vol 277 (3) ◽

pp. G678-G686 ◽

Cited By ~ 16

Author(s):

Yusuke Tando ◽

Hana Algül ◽

Martin Wagner ◽

Hans Weidenbach ◽

Guido Adler ◽

...

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Nuclear Translocation ◽

Inhibitory Effect ◽

Binding Activity ◽

Atpase Inhibitor ◽

Kinase C ◽

Protein Kinase C Activity ◽

Intracellular Ca ◽

Iκbα Degradation

The eukaryotic transcription factor NF-κB/Rel is activated by a large variety of stimuli. We have recently shown that NF-κB/Rel is induced during the course of caerulein pancreatitis. Here, we show that activation of NF-κB/Rel by caerulein, a CCK analog, requires increasing intracellular Ca2+ levels and protein kinase C activation. Caerulein induces a dose-dependent increase of nuclear NF-κB/Rel binding activity in pancreatic lobules, which is paralleled by degradation of IκBα. IκBβ was only slightly affected by caerulein treatment. Consistent with an involvement of Ca2+, the endoplasmic reticulum-resident Ca2+-ATPase inhibitor thapsigargin activated NF-κB/Rel in pancreatic lobules. The intracellular Ca2+ chelator TMB-8 prevented IκBα degradation and subsequent nuclear translocation of NF-κB/Rel induced by caerulein. BAPTA-AM was less effective. Cyclosporin A, a Ca2+/calmodulin-dependent protein phosphatase (PP2B) inhibitor, decreased caerulein-induced NF-κB/Rel activation and IκBα degradation. The inhibitory effect of bisindolylmaleimide suggests that protein kinase C activity is also required for caerulein-induced NF-κB/Rel activation. These data suggest that Ca2+- as well as protein kinase C-dependent mechanisms are required for caerulein-induced NF-κB/Rel activation.

Download Full-text

Physicochemical properties of calcium-binding protein isolated from rat liver cytosol: Ca2+-induced conformational changes.

Chemical and Pharmaceutical Bulletin ◽

10.1248/cpb.36.286 ◽

1988 ◽

Vol 36 (1) ◽

pp. 286-290 ◽

Cited By ~ 24

Author(s):

MASAYOSHI YAMAGUCHI

Keyword(s):

Physicochemical Properties ◽

Rat Liver ◽

Conformational Changes ◽

Calcium Binding ◽

Binding Protein ◽

Calcium Binding Protein ◽

Liver Cytosol ◽

Rat Liver Cytosol

Download Full-text

Involvement of calcium-sensitive phospholipid-dependent protein kinase in control of acid secretion by isolated rat parietal cells

Biochemical Journal ◽

10.1042/bj2320609 ◽

1985 ◽

Vol 232 (2) ◽

pp. 609-611 ◽

Cited By ~ 30

Author(s):

N G Anderson ◽

P J Hanson

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Acid Secretion ◽

Phorbol Esters ◽

Inhibitory Effect ◽

Dependent Protein Kinase ◽

Kinase C ◽

Protein Kinase C Activity ◽

Dependent Protein ◽

Isolated Rat

The relative potency with which phorbol esters inhibited histamine-stimulated aminopyrine accumulation (an index of acid secretion) paralleled that which has been established for the activation of purified protein kinase C. The inhibitory effect of 1-oleoyl-2-acetylglycerol on aminopyrine accumulation stimulated by various secretagogues was similar to that of 12-O-tetradecanoylphorbol 13-acetate. Protein kinase C activity was present in a parietal-cell-enriched fraction. In conclusion, protein kinase C could be involved in mechanisms regulating gastric acid secretion.

Download Full-text