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Characterization of the mechanisms involved in the gastric antisecretory effect of TLQP-21, a vgf-derived peptide, in rats

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Abstract

TLQP-21, a vgf-derived peptide modulates gastric emptying and prevents ethanol-induced gastric lesions in rats. However, it remains to be studied whether or not TLQP-21 affects gastric acid secretion. In this study, we evaluated the effects of central (0.8–8 nmol/rat) or peripheral (48–240 nmol/kg, intraperitoneally) TLQP-21 administration on gastric acid secretion in pylorus-ligated rats. The mechanisms involved in such activity were also examined. Central TLQP-21 injection significantly reduced gastric acid volume and dose-dependently inhibited total acid output (ED50 = 2.71 nmol), while peripheral TLQP-21 administration had no effect. The TLQP-21 antisecretory activity was prevented by cysteamine (300 mg/kg, subcutaneously), a depletor of somatostatin, by indomethacin (0.25 mg/rat, intracerebroventricularly), a non-selective cyclooxygenase inhibitor, and by functional ablation of sensory nerves by capsaicin. We conclude that TLQP-21 could be considered a new member of the large group of regulatory peptides affecting gastric acid secretion. The central inhibitory effect of TLQP-21 on gastric acid secretion is mediated by endogenous somatostatin and prostaglandins and requires the integrity of sensory nerve fibres.

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References

  • Abdel Salam OM, Mózsik G, Szolcsányi J (1995) Studies on the effect of intragastric capsaicin on gastric ulcer and on the prostacyclin-induced cytoprotection in rats. Pharmacol Res 32:209–215

    Article  PubMed  CAS  Google Scholar 

  • Bartolomucci A, La Corte G, Possenti R, Locatelli V, Rigamonti AE, Torsello A, Bresciani E, Bulgarelli I, Rizzi R, Pavone F, D’Amato FR, Severini C, Mignogna G, Giorgi A, Schininà ME, Elia G, Brancia C, Ferri GL, Conti R, Ciani B, Pascucci T, Dell’Omo G, Muller EE, Levi A, Moles A (2006) TLQP-21, a VGF-derived peptide, increases energy expenditure and prevents the early phase of diet-induced obesity. Proc Natl Acad Sci USA 103:14584–14589

    Article  PubMed  CAS  Google Scholar 

  • Bartolomucci A, Rigamonti AE, Bulgarelli I, Torsello A, Locatelli V, Pavone F, Levi A, Possenti R, Muller EE, Moles A (2007) Chronic intracerebroventricular TLQP-21 delivery does not modulate the GH/IGF-1-axis and muscle strength in mice. Growth Horm IGF Res 17:342–345

    Article  PubMed  CAS  Google Scholar 

  • Bartolomucci A, Moles A, Levi A, Possenti R (2008) Pathophysiological role of TLQP-21: gastrointestinal and metabolic functions. Eat Weight Disord 13:e49–e54

    PubMed  CAS  Google Scholar 

  • Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156–159

    Article  PubMed  CAS  Google Scholar 

  • Cocco C, Brancia C, Pirisi I, D’Amato F, Noli B, Possenti R, Ferri GL (2007) VGF metabolic-related gene: distribution of its derived peptides in mammalian pancreatic islets. J Histochem Cytochem 55:619–628

    Article  PubMed  CAS  Google Scholar 

  • Cowley MA, Smith RG, Diano S, Tschöp M, Pronchuk N, Grove KL, Strasburger CJ, Bidlingmaier M, Esterman M, Heiman ML, Garcia-Segura LM, Nillni EA, Mendez P, Low MJ, Sotonyi P, Friedman JM, Liu H, Pinto S, Colmers WF, Cone RD, Horvath TL (2003) The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis. Neuron 37:649–661

    Article  PubMed  CAS  Google Scholar 

  • Evangelista S, Renzi D, Tramontana M, Surrenti C, Theodorsson E, Maggi CA (1992) Cysteamine induced-duodenal ulcers are associated with a selective depletion in gastric and duodenal calcitonin gene-related peptide-like immunoreactivity in rats. Regul Pept 39:19–28

    Article  PubMed  CAS  Google Scholar 

  • Ferri GL, Levi A, Possenti R (1992) A novel neuroendocrine gene product: selective VGF8a gene expression and immuno-localisation of the VGF protein in endocrine and neuronal populations. Brain Res Mol Brain Res 13:139–143

    Article  PubMed  CAS  Google Scholar 

  • Hahm S, Mizuno TM, Wu TJ, Wisor JP, Priest CA, Kozak CA, Boozer CN, Peng B, McEvoy RC, Good P, Kelley KA, Takahashi JS, Pintar JE, Roberts JL, Mobbs CV, Salton SR (1999) Targeted deletion of the Vgf gene indicates that the encoded secretory peptide precursor plays a novel role in the regulation of energy balance. Neuron 23:537–548

    Article  PubMed  CAS  Google Scholar 

  • Horie S, Yamamoto H, Michael GJ, Uchida M, Belai A, Watanabe K, Priestley JV, Murayama T (2004) Protective role of vanilloid receptor type 1 in HCl-induced gastric mucosal lesions in rats. Scand J Gastroenterol 39:303–312

    Article  PubMed  CAS  Google Scholar 

  • Izbéki F, Wittmann T, Jancsó G, Csáti S, Lonovics J (2002) Inhibition of gastric emptying and small intestinal transit by ethanol is mediated by capsaicin-sensitive afferent nerves. Naunyn Schmiedebergs Arch Pharmacol 365:17–21

    Article  PubMed  Google Scholar 

  • Kanemasa K, Okamura H, Kodama T, Ibata Y (1995a) Induction of VGF mRNA in neurons of the rat nucleus tractus solitarius and the dorsal motor nucleus of vagus in duodenal ulceration by cysteamine. Brain Res Mol Brain Res 32:55–62

    Article  PubMed  CAS  Google Scholar 

  • Kanemasa K, Okamura H, Kodama T, Kashima K, Ibata Y (1995b) Time course of the induction of VGF mRNA in the dorsal vagal complex in rats with cysteamine-induced peptic ulcers. Brain Res Mol Brain Res 34:309–314

    Article  PubMed  CAS  Google Scholar 

  • Kawashima K, Ishihara S, Karim Rumi MA, Moriyama N, Kazumori H, Suetsugu H, Sato H, Fukuda R, Adachi K, Shibata M, Onodera S, Chiba T, Kinoshita Y (2002) Localization of calcitonin gene-related peptide receptors in rat gastric mucosa. Peptides 23:955–966

    Article  PubMed  CAS  Google Scholar 

  • Lambrecht NW, Yakubov I, Zer C, Sachs G (2006) Transcriptomes of purified gastric ECL and parietal cells: identification of a novel pathway regulating acid secretion. Physiol Genomics 25:153–165

    Article  PubMed  CAS  Google Scholar 

  • Levi A, Eldridge JD, Paterson BM (1985) Molecular cloning of a gene sequence regulated by nerve growth factor. Science 229:393–395

    Article  PubMed  CAS  Google Scholar 

  • Levi A, Ferri GL, Watson E, Possenti R, Salton SR (2004) Processing, distribution, and function of VGF, a neuronal and endocrine peptide precursor. Cell Mol Neurobiol 24:517–533

    Article  PubMed  CAS  Google Scholar 

  • Liu JW, Andrews PC, Mershon JL, Yan C, Allen DL, Ben-Jonathan N (1994) Peptide V: a VGF-derived neuropeptide purified from bovine posterior pituitary. Endocrinology 135:2742–2748

    Article  PubMed  CAS  Google Scholar 

  • Lu S, Guan JL, Wang QP, Uehara K, Yamada S, Goto N, Date Y, Nakazato M, Kojima M, Kangawa K, Shioda S (2002) Immunocytochemical observation of ghrelin-containing neurons in the rat arcuate nucleus. Neurosci Lett 321:157–160

    Article  PubMed  CAS  Google Scholar 

  • Mózsik G, Vincze A, Szolcsányi J (2001) Four response stages of capsaicin-sensitive primary afferent neurons to capsaicin and its analog: gastric acid secretion, gastric mucosal damage and protection. J Gastroenterol Hepatol 16:1093–1097

    Article  PubMed  Google Scholar 

  • Netti C, Bossa R, Galatulas I, Sibilia V, Pecile A (1984) Antinociceptive effect of centrally administered cimetidine and dimaprit in the rat. Pharmacology 28:262–267

    Article  PubMed  CAS  Google Scholar 

  • Possenti R, Eldridge JD, Paterson BM, Grasso A, Levi A (1989) A protein induced by NGF in PC12 cells is stored in secretory vesicles and released through the regulated pathway. EMBO J 8:2217–2223

    PubMed  CAS  Google Scholar 

  • Rindi G, Licini L, Necchi V, Bottarelli L, Campanini N, Azzoni C, Favret M, Giordano G, D’Amato F, Brancia C, Solcia E, Ferri GL (2007) Peptide products of the neurotrophin-inducible gene vgf are produced in human neuroendocrine cells from early development and increase in hyperplasia and neoplasia. J Clin Endocrinol Metab 92:2811–2815

    Article  PubMed  CAS  Google Scholar 

  • Sagar SM, Landry D, Millard WJ, Badger TM, Arnold MA, Martin JB (1982) Depletion of somatostatin-like immunoreactivity in the rat central nervous system by cysteamine. J Neurosci 2:225–231

    PubMed  CAS  Google Scholar 

  • Salton SR, Fischberg DJ, Dong KW (1991) Structure of the gene encoding VGF, a nervous system-specific mRNA that is rapidly and selectively induced by nerve growth factor in PC12 cells. Mol Cell Biol 11:2335–2349

    PubMed  CAS  Google Scholar 

  • Salton SR, Ferri GL, Hahm S, Snyder SE, Wilson AJ, Possenti R, Levi A (2000) VGF: a novel role for this neuronal and neuroendocrine polypeptide in the regulation of energy balance. Front Neuroendocrinol 21:199–219

    Article  PubMed  CAS  Google Scholar 

  • Sandvik AK, Dimaline R, Forster ER, Evans D, Dockray GJ (1993) Differential control of somatostatin messenger RNA in rat gastric corpus and antrum. Role of acid, food, and capsaicin-sensitive afferent neurons. J Clin Invest 91:244–250

    Article  PubMed  CAS  Google Scholar 

  • Sann H, Jancso G, Ambrus A, Piereau FK (1995) Capsaicin treatment induces selective sensory degeneration and increased sympathetic innervation in the rat ureter. Neuroscience 67:953–966

    Article  PubMed  CAS  Google Scholar 

  • Saperas E, Kauffman G, Taché Y (1991) Role of central prostaglandin E2 in the regulation of gastric acid secretion in the rat. Eur J Pharmacol 209:1–7

    Article  PubMed  CAS  Google Scholar 

  • Sautereau D, Chicau-Chovet M, Tsocas A, Rozé C (1991) Central and peripheral effects of prostaglandin E2 and enprostil on gastric acid secretion in the rat. Eur J Pharmacol 195:217–224

    Article  PubMed  CAS  Google Scholar 

  • Schubert ML (2003) Gastric secretion. Curr Opin Gastroenterol 19:519–525

    Article  PubMed  CAS  Google Scholar 

  • Schubert ML (2008) Gastric secretion. Curr Opin Gastroenterol 24:659–664

    Article  PubMed  Google Scholar 

  • Schubert ML, Peura DA (2008) Control of gastric acid secretion in health and disease. Gastroenterology 134:1842–1860

    Article  PubMed  CAS  Google Scholar 

  • Severini C, La Corte G, Improta G, Broccardo M, Agostini S, Petrella C, Sibilia V, Pagani F, Guidobono F, Bulgarelli I, Ferri GL, Brancia C, Rinaldi AM, Levi A, Possenti R (2009) In vitro and in vivo pharmacological role of TLQP-21, a VGF-derived peptide, in the regulation of rat gastric motor functions. Br J Pharmacol 157:984–993

    Article  PubMed  CAS  Google Scholar 

  • Shay H, Sun DC, Gruenstein M (1954) A quantitative method for measuring spontaneous gastric secretion in the rat. Gastroenterology 26:906–913

    PubMed  CAS  Google Scholar 

  • Sibilia V, Pagani F, Bulgarelli I, Mrak E, Broccardo M, Improta G, Severini C, Possenti R, Guidobono F (2010) TLQP-21, a VGF-derived peptide, prevents ethanol-induced gastric lesions: insights into its mode of action. Neuroendocrinology 92:189–197

    Article  PubMed  CAS  Google Scholar 

  • Snyder SE, Peng B, Pintar JE, Salton SR (2003) Expression of VGF mRNA in developing neuroendocrine and endocrine tissues. J Endocrinol 179:227–235

    Article  PubMed  CAS  Google Scholar 

  • Szabo S, Reichlin S (1981) Somatostatin in rat tissues is depleted by cysteamine administration. Endocrinology 109:2255–2257

    Article  PubMed  CAS  Google Scholar 

  • Szolcsányi J, Barthó L (2001) Capsaicin-sensitive afferents and their role in gastroprotection: an update. J Physiol Paris 95:181–188

    Article  PubMed  Google Scholar 

  • Taché Y, Yang H (1990) Brain regulation of gastric acid secretion by peptides Sites and mechanisms of action. Ann N Y Acad Sci 597:128–145

    Article  PubMed  Google Scholar 

  • Tebbe JJ, Dietze T, Grote C, Mönnikes H (2001) Excitatory stimulation of neurons in the arcuate nucleus inhibits gastric acid secretion via vagal pathways in anesthetized rats. Brain Res 913:10–17

    Article  PubMed  CAS  Google Scholar 

  • Trani E, Ciotti T, Rinaldi AM, Canu N, Ferri GL, Levi A, Possenti R (1995) Tissue-specific processing of the neuroendocrine protein VGF. J Neurochem 65:2441–2449

    Article  PubMed  CAS  Google Scholar 

  • Trani E, Giorgi A, Canu N, Amadoro G, Rinaldi AM, Halban PA, Ferri GL, Possenti R, Schininà ME, Levi A (2002) Isolation and characterization of VGF peptides in rat brain. Role of PC1/3 and PC2 in the maturation of VGF precursor. J Neurochem 81:565–574

    Article  PubMed  CAS  Google Scholar 

  • Yokotani K, Yokotani K, Okuma Y, Osumi Y (1988) Sympathoadrenomedullary system mediation of the prostaglandin E2-induced central inhibition of gastric acid output in rats. J Pharmacol Exp Ther 244:335–340

    PubMed  CAS  Google Scholar 

  • Yokotani K, Okuma Y, Osumi Y (1996) Inhibition of vagally mediated gastric acid secretion by activation of central prostanoid EP3 receptors in urethane-anaesthetized rats. Br J Pharmacol 117:653–656

    PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by funds from FIRST 2006 to VS.

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Authors and Affiliations

  1. Department of Pharmacology, Chemotherapy and Medical Toxicology, Università degli Studi di Milano, Via Vanvitelli, 32, 20129, Milan, Italy

    Valeria Sibilia, Francesca Pagani, Ilaria Bulgarelli & Francesca Guidobono

  2. Division of Pharmacology and Toxicology, Department of Biomedical Sciences and Biotechnology, Università degli Studi di Brescia, Brescia, Italy

    Giovanni Tulipano

  3. Institute of Neurobiology and Molecular Medicine, CNR, Via del Fosso di Fiorano 64/65, Rome, Italy

    Roberta Possenti

  4. Department of Neuroscience, University “Tor Vergata”, Rome, Italy

    Roberta Possenti

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  1. Valeria Sibilia
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  2. Francesca Pagani
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  3. Ilaria Bulgarelli
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  4. Giovanni Tulipano
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  5. Roberta Possenti
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  6. Francesca Guidobono
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Correspondence to Valeria Sibilia.

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Sibilia, V., Pagani, F., Bulgarelli, I. et al. Characterization of the mechanisms involved in the gastric antisecretory effect of TLQP-21, a vgf-derived peptide, in rats. Amino Acids 42, 1261–1268 (2012). https://doi.org/10.1007/s00726-010-0818-6

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