Presence and release of SR-17 (chromogranin B586–602) in the porcine splenic nerve and its enzymatic degradation by CD26/dipeptidyl peptidase IV

Depreitere, Jan; Durinx, Christine; Wang, Zesheng; Coen, Edmond; Lambeir, Anne‐Marie; Potter, W.P. De; Nouwen, Etienne J.

doi:10.1016/s0167-0115(02)00038-1

Cited by 7 publications

(2 citation statements)

References 38 publications

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“…DPP IV can cleave substrates such as eotaxin, regulated on activation normal T cell expressed and secreted (RANTES, CCL5), neuropeptide Y (NPY), substance P, chromogranin B - derived peptides, and other airway peptides [32,33]. Sitagliptin's inhibition of DPP IV activity may disrupt the normal functions of these polypeptides, particularly in inflamed mucosa [6].…”

Section: Discussionmentioning

confidence: 99%

Rhinorrhea, cough and fatigue in patients taking sitagliptin

Baraniuk

Jamieson

2010

All Asth Clin Immun

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Sitagliptin is a dipeptidyl peptidase-4 (DPP IV, CD26) inhibitor indicated for treatment of Type II diabetes as a second line therapy after metformin. We report fifteen sitagliptin intolerant patients who developed anterior and posterior rhinorrhea, cough, dyspnea, and fatigue. Symptoms typically developed within 1 to 8 weeks of starting, and resolved within 1 week of stopping the drug. Peak expiratory flow rates increased 34% in 8 patients who stopped sitagliptin. Similar changes were found in 4 out of 5 persons who had confirmatory readministration. Chart review identified 17 patients who tolerated sitagliptin and had no symptomatic changes. The sitagliptin intolerant group had higher rates of clinically diagnosed allergic rhinitis (15/15 vs. 6/18; p = 0.00005), Fisher's Exact test) and angiotensin converting enzyme inhibitor - induced cough (6/13 vs. 1/18; p = 0.012). Nasal and inhaled glucocorticoids may control the underlying allergic inflammation and abrogate this new sitagliptin - induced pharmacological syndrome. Potential mucosal and central nervous system mechanisms include disruption of neuropeptides and/or cytokines that rely on DPP IV for activation or inactivation, and T cell dysfunction.

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Section: Discussionmentioning

confidence: 99%

Rhinorrhea, cough and fatigue in patients taking sitagliptin

Baraniuk

Jamieson

2010

All Asth Clin Immun

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“…As a pro‐protein, CHGB is cleaved to the antibacterial peptide secretolytin (bovine CHGB 614−626 ) (Strub et al . 1995) and other peptides with undetermined biological functions, including SR‐17 (porcine CHGB 586−602 ) (Depreitere et al . 2002), CCB (human CHGB 597−653 ) (Benjannet et al .…”

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confidence: 99%

Molecular basis of neuroendocrine cell type‐specific expression of the chromogranin B gene: crucial role of the transcription factors CREB, AP‐2, Egr‐1 and Sp1

Mahapatra¹,

Mahata²,

Ghosh³

et al. 2006

Journal of Neurochemistry

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The molecular basis of neuroendocrine-specific expression of chromogranin B gene (Chgb) has remained elusive. Utilizing wild-type and mutant Chgb promoter/luciferase reporter constructs, this study established a crucial role for the cAMP response element (CRE) box at )102/)95 bp in endocrine [rat pheochromocytoma (chromaffin) cell line (PC12) and rat pituitary somatotrope cell line (GC)] and neuronal [rat dorsal root ganglion/mouse neuroblastoma hybrid cell line (F-11), cortical and hippocampal primary neurons] cells. Additionally, G/C-rich domains at )134/)127, )125/)117 and )115/)110 bp played especially important roles for endocrine-specific expression of the Chgb gene. Co-transfection of expression plasmids for CREB, activator protein-2 (transcription factor) (AP-2), early growth response protein (transcription factor) (Egr-1) or specificity protein 1 (transcription factor) (Sp1) with the Chgb promoter constructs trans-activated expression of the Chgb gene. Nuclear extracts from either PC12 or F-11 cells formed specific complexes with the Chgb ()110/)87 bp) (CRE) oligonucleotide, which were either supershifted or disrupted by anti-CREB antibodies. In addition PC12 nuclear extracts also formed a specific complex with a Chgb ()140/)104-bp) oligonucleotide containing three G/C-rich regions, which was dose-dependently disrupted by anti-AP-2, anti-Egr-1 or antiSp1 antibodies; indeed, any one of these three antibodies completely abolished the complex, suggesting that all three factors bind the region simultaneously, at least in vitro. Chromatin immunoprecipitation assays documented the binding of the transcription factors CREB, AP-2, Egr-1 and Sp1 to the chromosomal Chgb gene promoter in vivo in PC12 cells within the context of chromatin. We conclude that the neuroendocrine-specific expression of Chgb is mediated by the CRE and G/C boxes in cis and the transcription factors CREB, AP-2, Egr-1 and Sp1 in trans.

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