Involvement of Calmodulin and Protein Kinase C in Cholecystokinin Release by Bombesin from STC-1 Cells

Takahashi, Akira; Tanaka, Shigeki; Miwa, Yoshikatsu; Yoshida, Hitoshi; Ikegami, Akitoshi; Niikawa, Junichi; Mitamura, Keiji

doi:10.1097/00006676-200010000-00003

Cited by 8 publications

(9 citation statements)

References 33 publications

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“…While the involvement of fatty acid transporters in the glucoregulatory effects of intraduodenal lipids has not been tested, a likely role of fatty acid transporter cluster of differentiation 36 (CD36) is presented given that CD36 À/À mice exhibit a reduced satiety response as well as reduced CCK release in response to intestinal lipids Sundaresan et al, 2013) ( Figure 1). Furthermore, the glucose-lowering effect of LCFAs is mediated by the activation of duodenal protein kinase C (PKC)-d, which is expressed in rodent and human duodenal mucosa (Breen et al, 2011;Kokorovic et al, 2011), consistent with studies reporting that PKC-d mediates LCFA-induced CCK secretion from STC-1 cells (Chang et al, 2000;Takahashi et al, 2000). Although the downstream signaling events of PKC-d remain unclear, this glucose-lowering LCFA/LCFACoA/PKC-d axis requires activation of duodenal CCK-1 receptors (CCK-1R) (Breen et al, 2011;Cheung et al, 2009).…”

Section: Intestinal Nutrient Sensingsupporting

confidence: 73%

Glucoregulatory Relevance of Small Intestinal Nutrient Sensing in Physiology, Bariatric Surgery, and Pharmacology

et al. 2015

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Emerging evidence suggests the gastrointestinal tract plays an important glucoregulatory role. In this perspective, we first review how the intestine senses ingested nutrients, initiating crucial negative feedback mechanisms through a gut-brain neuronal axis to regulate glycemia, mainly via reduction in hepatic glucose production. We then highlight how intestinal energy sensory mechanisms are responsible for the glucose-lowering effects of bariatric surgery, specifically duodenal-jejunal bypass, and the antidiabetic agents metformin and resveratrol. A better understanding of these pathways lays the groundwork for intestinally targeted drug therapy for the treatment of diabetes.

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Section: Intestinal Nutrient Sensingsupporting

confidence: 73%

Glucoregulatory Relevance of Small Intestinal Nutrient Sensing in Physiology, Bariatric Surgery, and Pharmacology

et al. 2015

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“…Moore et al (38) reported that stimulation of G cells with BBS resulted in the translocation of PKC-␥ from a predominantly intracellular location to the plasma membrane. Another study, using the STC-1 cell line, demonstrated that CCK secretion in response to BBS involves MAPK activation through a PKC-dependent mechanism (50). We found that BBS-mediated NT secretion in the BON/ GRP-R cell line, similar to PMA stimulation, was inhibited by using the PKC inhibitors, including the specific PKC-␦ inhibitor rottlerin.…”

Section: Discussionmentioning

confidence: 59%

“…The conventional isoforms require both Ca 2ϩ and diacylglycerol (DAG), novel isoforms are Ca 2ϩ independent, and atypical isoforms are Ca 2ϩ independent and DAG or phorbol ester resistant (39,41). In endocrine cells, particularly in the pancreas and thyroid, PKC isoforms have been detected and linked to the regulation of hormone secretion (9,16,20,22,23,35,42,49,50,57). On activation, PKC isoforms translocate to new cellular sites, including the plasma membrane, cytoskeletal elements, and the nucleus, as well as other subcellular compartments (39,41).…”

mentioning

confidence: 99%

Phorbol ester-mediated neurotensin secretion is dependent on the PKC-α and -δ isoforms

Hellmich

Greeley

et al. 2002

American Journal of Physiology-Gastrointestinal and Liver Physi

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Neurotensin (NT) plays an important role in gastrointestinal secretion, motility, and growth. The mechanisms regulating NT secretion are not entirely known. Our purpose was to define the role of the PKC signaling pathway in secretion of NT from BON cells, a human pancreatic carcinoid cell line that produces and secretes NT peptide. We demonstrated expression of all 11 PKC isoforms at varying levels in untreated BON cells. Expression of PKC-α, -β2, -δ, and -μ isoforms was most pronounced. Immunofluorescent staining showed PKC-α and -μ expression throughout the cytoplasm and in the membrane. Also, significant fluorescence of PKC-δ was noted in the nucleus and cytoplasm. Treatment with PMA induced translocation of PKC-α, -δ, and -μ from cytosol to membrane. Activation of PKC-α, -δ, and -μ was further confirmed by kinase assays. Addition of PKC-α inhibitor Gö-6976 at a nanomolar concentration, other PKC inhibitors Gö-6983 and GF-109203X, or PKC-δ-specific inhibitor rottlerin significantly inhibited PMA-mediated NT release. Overexpression of either PKC-α or -δ increased PMA-mediated NT secretion compared with control cells. We demonstrated that PMA-mediated NT secretion in BON cells is associated with translocation and activation of PKC-α, -δ, and -μ. Furthermore, inhibition of PKC-α and -δ blocked PMA-stimulated NT secretion, suggesting a critical role for these isoforms in NT release.

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“…The biologically active DBI fragment DBI (33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50) induces Ca 2ϩ oscillations and CCK secretion in STC-1 cells (151). In addition to luminal factors, neuropeptide bombesin (101,131,136), ␤-adrenergic receptor agonist (127), GABA (44,54), and orexins (69) could all stimulate I cell CCK secretion. Both radioligand binding studies and Northern blot analyses suggested the presence of bombesin-like receptors in CCK cells (131).…”

Section: Gut Cck-secreting Cellmentioning

confidence: 99%

“…Both radioligand binding studies and Northern blot analyses suggested the presence of bombesin-like receptors in CCK cells (131). Bombesin-stimulated CCK secretion from STC-1 cells was PKC dependent and involved the MAPK pathway (101) and calmodulin (136). Liddle and colleagues (127) demonstrated the presence of ␤-adrenergic receptors in STC-1 cells, the stimulation of which led to cAMP production and CCK release (127).…”

Section: Gut Cck-secreting Cellmentioning

confidence: 99%

How does cholecystokinin stimulate exocrine pancreatic secretion? From birds, rodents, to humans

Wang¹,

Cui²

2007

American Journal of Physiology-Regulatory, Integrative and Comp

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Wang BJ, Cui ZJ. How does cholecystokinin stimulate exocrine pancreatic secretion? From birds, rodents, to humans. Am J Physiol Regul Integr Comp Physiol 292: R666-R678, 2007. First published October 19, 2006; doi:10.1152/ajpregu.00131.2006.-The field of cholecystokinin (CCK) stimulation of exocrine pancreatic secretion has experienced major changes in the recent past. This review attempts to summarize the present status of the field. CCK production in the intestinal I cells, the molecular forms of CCK produced and subsequently circulated in the blood, the presence or absence of CCK receptors on the isolated pancreatic acinar cells and the associated signaling for acinar cell secretion, and the actual circuits and sites of action for CCK regulation of exocrine pancreatic secretion in vivo are reviewed in different animal species with an emphasis on birds, rodents, and humans. Clear differences in the relative importance of neural and direct modes of CCK action on pancreatic acinar cells were identified. Rodents seem to be endowed with both modes of action, whereas in humans the neural mode may predominate. In birds, such as duck, the direct mode needs further assistance from pituitary adenylate cyclaseactivating peptide/VIP receptors. However, much further work needs to be directed to the neural mode to map out all sites of CCK action and details of the full circuits, and we foresee a major revival for this field of research in the near future. pancreatic acinar cells; vagal afferent nerves; plasma cholecystokinin concentration; species specificity IT IS GENERALLY ACCEPTED THAT cholecystokinin (CCK) as a gut hormone is an important endogenous secretagogue in exocrine pancreatic secretion. CCK also stimulates gallbladder contraction and enhances growth of the exocrine pancreas (63,115,138). CCK is produced and released by the intestinal mucosal I cells (78). This source of CCK may travel through the circulation to target tissues that include the exocrine pancreas and gallbladder (65,78). CCK peptides are also found in large quantities in neurons, but neuronal CCK contributes negligibly to CCK concentration in the circulation (118). This general picture has been changed drastically by the recent findings that CCK can also stimulate exocrine pancreatic secretion by the excitation of sensory nerves and vagovagal and enteropancreatic reflexes, and this may be the only pathway in humans (65, 105). In addition, major differences have been found in the traditional humoral pathway, depending on the animal species (35,149). Therefore, the purpose of this review is to present the current status of CCK regulation of exocrine pancreatic secretion with a particular emphasis on species specificity as shown in birds, rodents, and humans.

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Involvement of Calmodulin and Protein Kinase C in Cholecystokinin Release by Bombesin from STC-1 Cells

Cited by 8 publications

References 33 publications

Glucoregulatory Relevance of Small Intestinal Nutrient Sensing in Physiology, Bariatric Surgery, and Pharmacology

Glucoregulatory Relevance of Small Intestinal Nutrient Sensing in Physiology, Bariatric Surgery, and Pharmacology

Phorbol ester-mediated neurotensin secretion is dependent on the PKC-α and -δ isoforms

How does cholecystokinin stimulate exocrine pancreatic secretion? From birds, rodents, to humans

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