CD26 modulates nociception in mice via its dipeptidyl-peptidase IV activity

Guieu, Régis; Fenouillet, Emmanuel; Devaux, Christiane; Fajloun, Ziad; Carrega, Louis; Sabatier, Jean‐Marc; Sauze, Nicole; Marguet, Didier

doi:10.1016/j.bbr.2005.08.003

Cited by 45 publications

(24 citation statements)

References 23 publications

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“…After its release from duodenal cells, GIP is rapidly degraded at the N‐terminal to the truncated form GIP(3–42) by the enzyme dipeptidyl peptidase IV (DPP IV; for review see Mentlein,1999). DPP IV is present in the brain (Bernstein et al,1987; Mentzel et al,1996; Gallegos et al,1999; Mentlein,1999; Sakurada et al,2003; Guieu et al,2006), and the monoclonal antibody (3.65H) used in the present study recognizes the C‐terminal part of GIP and therefore will therefore detect both GIP and GIP(3–42). In the brain, DPP IV activity is highest in the substantia nigra, followed by cerebral cortex, and is lowest in the caudate putamen (Gallegos et al,1999).…”

Section: Discussionmentioning

confidence: 88%

Immunohistochemical distribution of glucose‐dependent insulinotropic polypeptide in the adult rat brain

Nyberg¹,

Jacobsson²,

Anderson³

et al. 2007

J of Neuroscience Research

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We have previously demonstrated that glucose-dependent insulinotropic polypeptide (GIP; gastric inhibitory polypeptide) is present in the adult rat hippocampus. This finding leads to the conclusion that all members of the secretin-glucagon family of gastrointestinal regulatory polypeptides can be found in the brain. To investigate the localization of GIP-producing cells, we used immunohistochemistry on sections of the adult rat brain. High levels of GIP immunoreactivity were observed in the olfactory bulb, hippocampus, and Purkinje cells in the cerebellum. Moreover, a moderate but distinct GIP immunoreactivity was observed in the cerebral cortex, amygdala, substantia nigra, and lateral septal nucleus as well as in several nuclei in the thalamus, hypothalamus, and brainstem. GIP immunoreactivity was frequently found to colocalize with the neuronal marker NeuN but never with the glial marker glial fibrillary acidic protein. Thus, GIP appears to be mainly neuronal to its distribution. This widespread distribution of GIP-immunoreactive cells suggests the involvement of GIP in various neuronal functions and suggests that GIP may act as a neurotransmitter or neuromodulator. This is the first characterization of the anatomical distribution of GIP-immunoreactive cells in the rat brain providing an anatomical framework for future investigations regarding the functions of GIP in the central nervous system.

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Section: Discussionmentioning

confidence: 88%

Immunohistochemical distribution of glucose‐dependent insulinotropic polypeptide in the adult rat brain

Nyberg¹,

Jacobsson²,

Anderson³

et al. 2007

J of Neuroscience Research

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“…DPPIVϪ mice in C57BL/6 background were 6 to 8 weeks old when used and were originally provided by Dr. D. Marguet (INSERM, Marseilles, France). 17 Cell donors were 8-week-old to 15-week-old C57BL/6 mice from the National Cancer Institute (Bethesda, MD). Hepatocytes were isolated by 2-step collagenase perfusion, and 2 ϫ 10 6 viable cells were injected immediately in 0.2 mL RPMI 1640 medium into the splenic pulp as described.…”

Section: Methodsmentioning

confidence: 99%

Hepatocyte transplantation and drug-induced perturbations in liver cell compartments

Wu¹,

Joseph²,

Berishvili³

et al. 2008

Hepatology

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The potential for organ damage after using drugs or chemicals is a critical issue in medicine. To delineate mechanisms of drug-induced hepatic injury, we used transplanted cells as reporters in dipeptidyl peptidase IV-deficient mice. These mice were given phenytoin and rifampicin for 3 days, after which monocrotaline was given followed 1 day later by intrasplenic transplantation of healthy C57BL/6 mouse hepatocytes. We examined endothelial and hepatic damage by serologic or tissue studies and assessed changes in transplanted cell engraftment and liver repopulation by histochemical staining for dipeptidyl peptidase IV. Monocrotaline caused denudation of the hepatic sinusoidal endothelium and increased serum hyaluronic acid levels, along with superior transplanted cell engraftment. Together, phenytoin, rifampicin, and monocrotaline caused further endothelial damage, reflected by greater improvement in cell engraftment. Phenytoin, rifampicin, and monocrotaline produced injury in hepatocytes that was not apparent after conventional tissue studies. This led to transplanted cell proliferation and extensive liver repopulation over several weeks, which was more efficient in males compared with females, including greater induction by phenytoin and rifampicin of cytochrome P450 3A4 isoform that converts monocrotaline to toxic intermediates. Through this and other possible mechanisms, monocrotaline-induced injury in the endothelial compartment was retargeted to simultaneously involve hepatocytes over the long term. Moreover, after this hepatic injury, native liver cells were more susceptible to additional pro-oxidant injury through thyroid hormone, which accelerated the kinetics of liver repopulation. Conclusion: Transplanted reporter cells will be useful for obtaining insights into homeostatic mechanisms involving liver cell compartments, whereas targeted injury in hepatic endothelial and parenchymal cells with suitable drugs will also help advance liver cell therapy. ( T o obtain fresh paradigms in tissue homeostasis after exposure to drugs or chemicals, 1 we considered that reporter cells will help elucidate perturbations in the liver, because genetically marked reporter cells can be inserted into liver compartments, including the parenchyma or hepatic endothelium. 2-4 It was noteworthy that transplanted cells did not proliferate in the normal liver, where cell turnover is minimal, although, depending on the extent of injury in native cells, proliferation in healthy transplanted cells was activated. 5,6 In this way, transplanted cells could repopulate the liver, where in specific situations the kinetics of liver repopulation reflected loss of native hepatocytes. [7][8][9] In healthy animals, genotoxic manipulations were particularly effective in promoting such liver repopulation with healthy cells. However, further insights are necessary to obtain pharmacologic approaches for repopulating the liver, particularly for clinical applications.To develop cell compartment-specific hepatic perturbations, we used monocrotaline (...

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“…Plasma from wild-type (but not Fischer 344) rats cleaves recombinant SP [1][2][3][4][5][6][7][8][9][10][11] to generate SP [3][4][5][6][7][8][9][10][11] and SP [5][6][7][8][9][10][11], via mechanisms sensitive to the DPP4 inhibitor diprotin A (131). Dpp4 Ϫ/Ϫ mice exhibit approximately 2-fold higher levels of circulating SP, implicating an essential biological role for DPP4 in control of SP biology (132). Although potentiation of SP activity has been postulated to underlie the pathophysiology of nasopharyngitis or neurogenic inflammation occasionally reported with use of DPP4 inhibitors, SP is also rapidly cleaved by angiotensin-converting enzyme and neutral endopeptidase, and levels of intact vs cleaved SP are very low and difficult to quantify in vivo.…”

Section: U Substance P (Sp)mentioning

confidence: 99%

Pharmacology, Physiology, and Mechanisms of Action of Dipeptidyl Peptidase-4 Inhibitors

2014

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Dipeptidyl peptidase-4 (DPP4) is a widely expressed enzyme transducing actions through an anchored transmembrane molecule and a soluble circulating protein. Both membrane-associated and soluble DPP4 exert catalytic activity, cleaving proteins containing a position 2 alanine or proline. DPP4-mediated enzymatic cleavage alternatively inactivates peptides or generates new bioactive moieties that may exert competing or novel activities. The widespread use of selective DPP4 inhibitors for the treatment of type 2 diabetes has heightened interest in the molecular mechanisms through which DPP4 inhibitors exert their pleiotropic actions. Here we review the biology of DPP4 with a focus on: 1) identification of pharmacological vs physiological DPP4 substrates; and 2) elucidation of mechanisms of actions of DPP4 in studies employing genetic elimination or chemical reduction of DPP4 activity. We review data identifying the roles of key DPP4 substrates in transducing the glucoregulatory, anti-inflammatory, and cardiometabolic actions of DPP4 inhibitors in both preclinical and clinical studies. Finally, we highlight experimental pitfalls and technical challenges encountered in studies designed to understand the mechanisms of action and downstream targets activated by inhibition of DPP4.

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CD26 modulates nociception in mice via its dipeptidyl-peptidase IV activity

Cited by 45 publications

References 23 publications

Immunohistochemical distribution of glucose‐dependent insulinotropic polypeptide in the adult rat brain

Immunohistochemical distribution of glucose‐dependent insulinotropic polypeptide in the adult rat brain

Hepatocyte transplantation and drug-induced perturbations in liver cell compartments

Pharmacology, Physiology, and Mechanisms of Action of Dipeptidyl Peptidase-4 Inhibitors

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