Catabolism of gastrin releasing peptide and substance P by gastric membrane-bound peptidases

Bunnett, Nigel W.; Kobayashi, Rei; Orloff, Mark S.; Reeve, Joseph R.; Turner, Anthony J.; Walsh, John H.

doi:10.1016/0196-9781(85)90052-x

Cited by 47 publications

(27 citation statements)

References 20 publications

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“…In earlier studies, a phosphoramidon inhibitable membrane bound peptidase from gastric tissue with characteristics of NEP was reported to cleave a dipeptide from neuromedin C [GRP-(18-27)] after prolonged incubation (42,43). We find that CD10/NEP rapidly inactivates each of the BLP family Cell Biology: Shipp et al…”

mentioning

confidence: 65%

CD10/neutral endopeptidase 24.11 hydrolyzes bombesin-like peptides and regulates the growth of small cell carcinomas of the lung.

Shipp

Tarr

Chen

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

189

163

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mentioning

confidence: 65%

CD10/neutral endopeptidase 24.11 hydrolyzes bombesin-like peptides and regulates the growth of small cell carcinomas of the lung.

Shipp

Tarr

Chen

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

189

163

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“…In contrast with the high specificity of acetylcholinesterase, NEP degrades several peptides, albeit with graded affinity. Preferred residues in the P1h site are hydrophobic, such as Phe, Leu, Val, Tyr and Trp, and favourable substrates include substance P (SP), enkephalins, gastrinreleasing peptide, somatostatin, cholecystokinin and bradykinin [24][25][26][27]. However, the affinity of NEP for its substrate peptides is far lower than those of receptors for neuropeptides.…”

Section: Degradation Of Peptide Hormones and Neurotransmittersmentioning

confidence: 99%

Regulatory mechanisms that modulate signalling by G-protein-coupled receptors

Böhm

Grady

Bunnett

1997

Biochemical Journal

476

322

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The large and functionally diverse group of G-protein-coupled receptors includes receptors for many different signalling molecules, including peptide and non-peptide hormones and neurotransmitters, chemokines, prostanoids and proteinases. Their principal function is to transmit information about the extracellular environment to the interior of the cell by interacting with the heterotrimeric G-proteins, and they thereby participate in many aspects of regulation. Cellular responses to agonists of these receptors are usually rapidly attenuated. Mechanisms of signal attenuation include removal of agonists from the extracellular fluid, receptor desensitization, endocytosis and downregulation. Agonists are removed by dilution, uptake by transporters and enzymic degradation. Receptor desensitization is mediated by receptor phosphorylation by G-protein receptor kinases and second-messenger kinases, interaction of phosphorylated receptors with arrestins and receptor uncoupling from

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“…CD1O/NEP downregulates neurogenic inflammation ofthe lung by modulating locally effective concentrations of tachykinins (7)(8)(9)(10). The enzyme has been found to hydrolyze bombesin-like peptides (BLPs) within the conserved seven amino acid terminus required for biological activity (reviewed in 11,12,13 ). Recently, hydrolysis of BLPs by CD10/ NEP was demonstrated to modulate autocrine growth of small cell carcinomas ofthe lung (SCLCs): inhibition ofCD10/NEP stimulated the growth of BLP-responsive SCLCs and addition of CD10/NEP inhibited the growth of SCLC in a dose-dependent fashion ( 12).…”

Section: Introductionmentioning

confidence: 99%

CD10/neutral endopeptidase 24.11 regulates fetal lung growth and maturation in utero by potentiating endogenous bombesin-like peptides.

King¹,

Hua²,

Torday³

et al. 1993

J. Clin. Invest.

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Bombesin-like peptides (BLPs) are mitogens for bronchial epithelial cells and small cell lung carcinomas, and increase fetal lung growth and maturation in utero and in organ cultures. BLPs are hydrolyzed by the enzyme CD10/neutral endopeptidase 24.11 (CD10/NEP) which is expressed in bronchial epithelium and functions to inhibit BLP-mediated growth of small cell lung carcinomas. To determine whether CDI0/NEP regulates peptide-mediated lung development, we administered a specific CD1O/NEP inhibitor, SCH32615, to fetal mice in utero from gestational days e15-17. Fetal lung tissues were evaluated on el8 for: (a) growth using [3HIthymidine incorporation into nuclear DNA; and (b) maturation using: 13H1-choline incorporation into surfactant phospholipids, electron microscopy for type II pneumocytes, and Northern blot analyses for surfactant apoproteins A, B, and C. Inhibition of CD10 / NEP stimulated [3HIthymidine incorporation into DNA (70% above baseline, P < 0.005), 13Hlcholine incorporation into surfactant phospholipids (38% above baseline, P < 0.005), increased numbers of type II pneumocytes (36% above baseline, P = 0.07), and fivefold higher surfactant protein A transcripts (P < 0.05). CD10/NEP-mediated effects were completely blocked by the specific bombesin receptor antagonist, IDPhe'2, Leu14jbombesin. These observations suggest that CD10/NEP regulates fetal lung growth and maturation mediated by endogenous BLPs. (J. Clin. Invest. 1993. 91:1969-1973.) Key words: metalloendopeptidase * autocrine growth factors * fetal lung development * cell surface enzyme * common acute lymphoblastic leukemia antigen

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Catabolism of gastrin releasing peptide and substance P by gastric membrane-bound peptidases

Cited by 47 publications

References 20 publications

CD10/neutral endopeptidase 24.11 hydrolyzes bombesin-like peptides and regulates the growth of small cell carcinomas of the lung.

CD10/neutral endopeptidase 24.11 hydrolyzes bombesin-like peptides and regulates the growth of small cell carcinomas of the lung.

Regulatory mechanisms that modulate signalling by G-protein-coupled receptors

CD10/neutral endopeptidase 24.11 regulates fetal lung growth and maturation in utero by potentiating endogenous bombesin-like peptides.

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