Neural regulation of pancreatic hormone secretion by the C-terminal tetrapeptide of CCK

Rehfeld, Jens F.; Larsson, Lars‐Inge; Goltermann, N.; Schwartz, Thue W.; Holst, Jens J.; Jensen, S. L.; Morley, J. S.

doi:10.1038/284033a0

Cited by 231 publications

(116 citation statements)

References 31 publications

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“…Infusion of arginine also showed a similar effect, suggesting that amino acid(s) can inhibit PP release indirectly via the vagus nerve. Amino acids are known PP secretagogues in in vitro studies using the isolated perfused porcine [5] or canine [6] pancreas or pancreatic tissue slices [7]. However, these in vitro data are in contrast with the failure to demonstrate increased plasma PP concentrations in man [8] and pig [9], including our canine study in vivo, but are in accordance with the present results after vagotomy.…”

Section: Discussionsupporting

confidence: 88%

Effects of amino acids on pancreatic polypeptide before and after vagotomy in the dog

et al. 1986

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Summary.We have previously indicated a marked influence of the vagus nerve on postprandial pancreatic polypeptide secretion. The present study was designed to determine whether the vagus nerve also plays a role in the regulation of pancreatic polypeptide secretion by absorbed nutrients. The pancreatic polypeptide responses to 17 intravenously administered amino acids, as well as arginine and glucose, were measured and compared with those 1 year after truncal vagotomy in conscious dogs. In response to the infusion of a mixture of amino acids (20g during 60min), plasma pancreatic polypeptide concentrations decreased in normal dogs. The effect was, however, completely reversed by vagotomy, with a significant pancreatic polypeptide release being observed (p < 0.05). Arginine (5 g during 60 rain) also showed a similar, although not statistically significant, effect. After intravenous bolus-injection of glucose (0.5 g/kg body weight), a transient decrease of pancreatic polypeptide secretion was found; vagotomy abolished this response. These results suggest that the vagus nerve may have a suppressive role in the process of pancreatic polypeptide secretion induced by intravenous amino acid(s) and glucose.Key words: Pancreatic polypeptide, vagotomy, amino acids.Pancreatic polypeptide (PP) is a 36-amino acid linear polypeptide derived primarily from the pancreas. So far, data concerning PP release are consistent with the hypothesis that vagal cholinergic innervation of the pancreas is necessary for effective release of this peptide. Activation of vagal cholinergic mechanisms results in PP release.PP is released by food, especially by protein rich meals in a biphasic pattern. This postprandial PP response is mediated both by vagal and non-vagal cholinergic mechanisms. Muscarinic cholinergic-neural transmission must be involved [1][2]. However, studies of the effects of absorbed nutrients on PP secretion are few and still inconsistent, with discrepancies between in vivo and in vitro investigations being reported. Therefore, the purpose of this study was to evaluate the influence of the vagus nerve on PP secretion by intravenously administered amino acid(s) and glucose. Materials and methods Experimental protocolsSix adult mongrel dogs weighing about 12 kg were used for the study. All were healthy, well-conditioned, and fasted for 16 h before the experiment. Indwelling butterfly needles were inserted in each vein of the two forelegs. Blood samples were collected at -20, -10, 0, and between 5 (or 2.5) and 120min. The following three protocols were performed in each dog while in the conscious state: (a) Intravenous administration of 17 amino acids: 20 g of an L-amino acid solution in 0.21 (12% Ispol, Daigo, Japan) was infused at a constant rate for 60 rain. (b) Intravenous administration of arginine: 5 g of L-arginine in 0.21 saline (0.9%) was infused at a constant rate for 60 rain. (c) Intravenous administration of glucose: glucose, 0.5 g/kg body wt., 25% solution, was injected as a bolus within 30 s.After completion of these...

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Section: Discussionsupporting

confidence: 88%

Effects of amino acids on pancreatic polypeptide before and after vagotomy in the dog

et al. 1986

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“…This suggests that nitric oxide nerves participate in the regulation of islet function, which is supported by the finding that inhibition of nitric oxide synthase inhibits insulin secretion induced by 2-DG in mice [114]. Furthermore, cholecystokinin is also localised to islet nerves [115]. The CCK nerves might be of importance for insulin secretion because CCK is a potent stimulator of insulin secretion through activation of CCK-A receptors; the insulinotropic activation of CCK is mediated by PLC and PLA 2 [33,116].…”

Section: Other Nervesmentioning

confidence: 64%

Autonomic regulation of islet hormone secretion - Implications for health and disease

2000

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“…A selective receptor for glycine-extended gastrin has been described on the rat pancreatic carcinoma cell line AR4-2J (36). Singh et al (37) describe a "novel" gastrin receptor, and Rehfeld et al (38) show that specific binding sites for the COOH-terminal tetrapeptide of CCK or G17 exist on hog pancreatic islets. We have also identified specific binding sites for the COOH-terminal heptapeptide of gastrin on U373 human glioblastoma cells (16), which do not express CCK A or CCK B receptors (14,16,17,34) but do express CCK C receptor (34).…”

Section: Introductionmentioning

confidence: 99%

Characterization of Gastrin-Induced Proangiogenic Effects In vivo in Orthotopic U373 Experimental Human Glioblastomas and In vitro in Human Umbilical Vein Endothelial Cells

Lefranc¹,

Mijatovic

Mathieu

et al. 2004

Clinical Cancer Research

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Purpose: This study aims to investigate the role of gastrin-17 (G17) on angiogenesis features in gliomas both in vitro and in vivo.Experimental Design: The influences of G17 and G17 receptor antagonists were characterized in vitro in terms of angiogenesis on human umbilical vein endothelial cell (HUVEC) tubulogenesis processes on Matrigel and in vivo with respect to U373 orthotopic glioma xenografts. The influence of phosphatidylinositol 3-kinase, protein kinase C, and nuclear factor-B inhibitors was characterized in vitro on G17-mediated HUVEC tubulogenesis. G17-mediated release of interleukin (IL)-8 from HUVECs and G17-induced modifications in nuclear factor-B DNA binding activity were characterized by means of specific enzyme-linked immunosorbent assays. The influence of G17 on E-and Pselectin expression was determined by means of computerassisted microscopy, whereas the influence of E-and P-selectin on HUVEC migration was approached by means of antisense oligonucleotides. The chemotactic influence of G17 and IL-8 on HUVEC migration was characterized by means of computer-assisted videomicroscopy with Dunn chambers.Results: Messenger RNAs for cholecystokinin (CCK) A , CCK B , and CCK C receptors were present in HUVECs and microvessels dissected from a human glioblastoma. Whereas G17 significantly increased the levels of angiogenesis in vivo in the U373 experimental glioma model and in vitro in the HUVECs, the CCK B receptor antagonist L365,260 significantly counteracted the G17-mediated proangiogenic effects. G17 chemoattracted HUVECs, whereas IL-8 failed to do so. IL-8 receptor ␣ (CXCR1) and IL-8 receptor ␤ (CXCR2) mRNAs were not detected in these endothelial cells. Gastrin significantly (but only transiently) decreased the level of expression of E-selectin, but not P-selectin, whereas IL-8 increased the expression of E-selectin. Specific antisense oligonucleotides against E-and P-selectin significantly decreased HUVEC tubulogenesis processes in vitro on Matrigel.Conclusions: The present study shows that gastrin has marked proangiogenic effects in vivo on experimental gliomas and in vitro on HUVECs. This effect depends in part on the level of E-selectin activation, but not on IL-8 expression/ release by HUVECs.

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Neural regulation of pancreatic hormone secretion by the C-terminal tetrapeptide of CCK

Cited by 231 publications

References 31 publications

Effects of amino acids on pancreatic polypeptide before and after vagotomy in the dog

Effects of amino acids on pancreatic polypeptide before and after vagotomy in the dog

Autonomic regulation of islet hormone secretion - Implications for health and disease

Characterization of Gastrin-Induced Proangiogenic Effects In vivo in Orthotopic U373 Experimental Human Glioblastomas and In vitro in Human Umbilical Vein Endothelial Cells

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