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Effects of ghrelin on gastric distension sensitive neurons and gastric motility in the lateral septum and arcuate nucleus regulation

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Abstract

Background

Ghrelin is an endogenous ligand for the growth hormone secretagogue receptor (GHS-R) and a peptide hormone that promotes food intake and gastric motility. Our aims are to explore the effects of ghrelin on gastric distension (GD) sensitive neurons in the lateral septum, and the possible regulation of gastric motility by ghrelin through the hypothalamic arcuate nucleus (ARC).

Methods

Single-unit discharges were recorded, extracellularly, and the gastric motility was monitored by the administration of ghrelin in the lateral septum. The projection of nerve fiber and expression of ghrelin were observed by retrograde tracer and fluo-immunohistochemistry staining. The expression of GHS-R and ghrelin was determined by real-time polymerase chain reaction and western blotting analysis.

Results

There were GD neurons in the lateral septum. The administration of ghrelin could excite both GD-excitatory (GD-E) and GD-inhibitory (GD-I) neurons in the lateral septum. Gastric motility was significantly enhanced by the administration of ghrelin in the lateral septum in a dose-dependent manner. Pretreatment with [d-Lys-3]-GHRP-6, however, could completely abolish the ghrelin-induced effects. Electrical stimulation of the ARC could significantly excite the response of GD neurons to ghrelin, increase ghrelin protein expression in the lateral septum and promote gastric motility. Nevertheless, these effects could be mitigated by pretreatment of [d-Lys-3]-GHRP-6. Electrical lesion of the lateral septum resulted in decreased gastric motility. The GHS-R and Ghrelin/FG-double labeled neurons were observed in the lateral septum and ARC, respectively.

Conclusions

It is suggested that the lateral septum may receive afferent information from the gastrointestinal tract and promote gastric motility. Ghrelin plays an important role in promoting gastric motility in the lateral septum. The ARC may be involved in the regulation of the lateral septum’s influence on gastric motility.

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References

  1. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 1999;402:656–60.

    Article  CAS  PubMed  Google Scholar 

  2. Kojima M, Hosoda H, Matsuo H, Kangawa K. Ghrelin: discovery of the natural endogenous ligand for the growth hormone secretagogue receptor. Trends Endocrinol Metab. 2001;12:118–22.

    Article  CAS  PubMed  Google Scholar 

  3. Gnanapavan S, Kola B, Bustin SA, Morris DG, McGee P, Fairclough P, et al. The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. J Clin Endocrinol Metab. 2002;87:2988–91.

    Article  CAS  PubMed  Google Scholar 

  4. Cowley MA, Smith RG, Diano S, Tschöp M, Pronchuk N, Grove KL, et al. The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis. Neuron. 2003;37:649–61.

    Article  CAS  PubMed  Google Scholar 

  5. Morpurgo PS, Cappiello V, Verga U, Vicentini L, Vaghi I, Lauri E, et al. Ghrelin in human medullary thyroid carcinomas. Clin Endocrinol. 2005;63:437–41.

    Article  CAS  Google Scholar 

  6. Van der Lely AJ, Tschöp M, Heiman ML, Ghigo E. Biological, physiological, pathophysiological, and pharmacological aspects of ghrelin. Endocr Rev. 2004;25:426–57.

    Article  PubMed  Google Scholar 

  7. Korbonits M, Goldstone AP, Gueorguiev M, Grossman AB. Ghrelin-a hormone with multiple functions. Front Neuroendocrinol. 2004;25:27–68.

    Article  CAS  PubMed  Google Scholar 

  8. Ghigo E, Broglio F, Arvat E, Maccario M, Papotti M, Muccioli G. Ghrelin: more than a natural GH secretagogue and/or an orexigenic factor. Clin Endocrinol(Oxf). 2005;62:1–17.

    Google Scholar 

  9. Grove KL, Cowley MA. Is ghrelin a signal for the development of metabolic systems? J Clin Invest. 2005;115:3393–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Horvath TL, Diano S, Sotonyi P, Heiman M, Tschöp M. Minireview: ghrelin and the regulation of energy balance-a hypothalamic perspective. Endocrinology. 2001;142:4163–9.

    CAS  PubMed  Google Scholar 

  11. Fujino K, Inui A, Asakawa A, Kihara N, Fujimura M, Fujimiya M. Ghrelin induces fasted motor activity of the gastrointestinal tract in conscious fed rats. J Physiol. 2003;550:227–40.

    Article  CAS  PubMed  Google Scholar 

  12. Kitazawa T, De Smet B, Verbeke K, Depoortere I, Peeters TL. Gastric motor effects of peptide and non-peptide ghrelin agonists in mice in vivo and in vitro. Gut. 2005;54:1078–84.

    Article  CAS  PubMed  Google Scholar 

  13. Perboni S, Inui A. Appetite and gastrointestinal motility: role of ghrelin-family peptides. Clin Nutr. 2010;29:227–34.

    Article  CAS  PubMed  Google Scholar 

  14. Fujimiya M, Asakawa A, Ataka K, Kato I, Inui A. Different effects of ghrelin, des-acyl ghrelin and obestatin on gastroduodenal motility in conscious rats. World J Gastroenterol. 2008;14:6318–26.

    Article  PubMed  Google Scholar 

  15. Trudel L, Tomasetto C, Rio MC, Bouin M, Plourde V, Eberling P, et al. Ghrelin/motilin-related peptide is a potent prokinetic to reverse gastric postopera-tive ileus in rat. Am J Physiol Gastrointest Liver Physiol. 2002;282:G948–52.

    CAS  PubMed  Google Scholar 

  16. Edholm T. Ghrelin stimulates motility in the small intestine of rats through intrinsic cholinergic neurons. Regul Pept. 2004;121:25–30.

    Article  CAS  PubMed  Google Scholar 

  17. Davenport AP, Bonner TI, Foord SM, Harmar AJ, Neubig RR, Pin JP, Spedding M, et al. International Union of Pharmacology. LVI. Ghrelin receptor nomenclature, distribution, and function. Pharmacol Rev. 2005;57:541–6.

    Article  CAS  PubMed  Google Scholar 

  18. Diéguez C, da Boit K, Novelle MG, Martínez de Morentin PB, Nogueiras R, et al. New insights in ghrelin orexigenic effect. Front Horm Res. 2010;38:196–205.

    Article  PubMed  Google Scholar 

  19. Shioda S, Takenoya F, Yagi M, Wang L, Hori Y, Kageyama H. Neural networks of several novel neuropeptides involved in feeding regulation. Nutrition. 2008;24:848–53.

    Article  CAS  PubMed  Google Scholar 

  20. Hewson AK, Tung LY, Connell DW, Tookman L, Dickson SL. The rat arcuate nucleus integrates peripheral signals provided by leptin, insulin, and a ghrelin mimetic. Diabetes. 2002;51:3412–9.

    Article  CAS  PubMed  Google Scholar 

  21. Cone RD, Cowley MA, Butler AA, Fan W, Marks DL, Low MJ. The arcuate nucleus as a conduit for diverse signals relevant to energy homeostasis. Int J Obes Relat Metab Disord. 2001;25(Suppl 5):S63–7.

    Article  CAS  PubMed  Google Scholar 

  22. Currie PJ, Mirza A, Fuld R, Park D, Vasselli JR. Ghrelin is an orexigenic and metabolic signaling peptide in the arcuate and paraventricular nuclei. Am J Physiol Regul Integr Comp Physiol. 2005;289:R353–8.

    Article  CAS  PubMed  Google Scholar 

  23. Scopinho AA, Resstel LB, Corrêa FM. alpha(1)-Adrenoceptors in the lateral septal area modulate food intake behavior in rats. Br J Pharmacol. 2008;155:752–6.

    Article  CAS  PubMed  Google Scholar 

  24. de Arruda Camargo GM, de Arruda Camargo LA, Saad WA. On a possible dual role for the lateral septal area 5-HT(1A) receptor system in the regulation of water intake and urinary excretion. Behav Brain Res. 2010;215:122–8.

  25. Paxinos G, Watson C. The rat brain in steriotaxic coordinates. San Diego: Academic Press; 1998.

    Google Scholar 

  26. Xu L, Sun X, Depoortere I, Lu J, Guo F, Peeters TL. Effect of motilin on the discharge of rat hippocampal neurons responding to gastric distension and its potential mechanism. Peptides. 2008;29:585–92.

    Article  CAS  PubMed  Google Scholar 

  27. Jhamandas JH, Lind RW, Renau LP. Angiotensin II may mediate excitatory neurotransmission from the subfornical organ to the hypothalamic supraoptic nucleus: an anatomical and electrophysiological study in the rat. Brain Res. 1989;487:52–6.

    Article  CAS  PubMed  Google Scholar 

  28. Guan Y, Tang M, Jiang Z, Peeters TL. Excitatory effects of motilin in the hippocampus on gastric motility in rats. Brain Res. 2003;984:33–41.

    Article  CAS  PubMed  Google Scholar 

  29. Brisch R, Bernstein HG, Dobrowolny H, Krell D, Stauch R, Trübner K, et al. A morphometric analysis of the septal nuclei in schizophrenia and affective disorders: reduced neuronal density in the lateral septal nuclei in bipolar disorder. Eur Arch Psychiatry Clin Neurosci. 2011;261:47–58.

    Article  PubMed  Google Scholar 

  30. Jakab RL, Leranth C. “Septum.” In: Paxinos G, editor. The rat nervous system. 3rd ed. San Diego: Academic Press; 2004.

  31. Majeed NH, Przewłocka B, Wedzony K, Przewłocki R. Stimulation of food intake following opioid microinjection into the nucleus accumbens septi in rats. Peptides. 1986;7:711–6.

    Article  CAS  PubMed  Google Scholar 

  32. Wren AM, Seal LJ, Cohen MA, Brynes AE, Frost GS, Murphy KG, et al. Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab. 2001;86:5992.

    Article  CAS  PubMed  Google Scholar 

  33. Taniguchi H, Ariga H, Zheng J, Ludwig K, Takahashi T. Effects of ghrelin on interdigestive contractions of the rat gastrointestinal tract. World J Gastroenterol. 2008;14:6299–302.

    Article  CAS  PubMed  Google Scholar 

  34. Taniguchi H, Ariga H, Zheng J, Ludwig K, Mantyh C, Pappas TN, et al. Endogenous ghrelin and 5-HT regulate interdigestive gastrointestinal contractions in conscious rats. Am J Physiol Gastrointest Liver Physiol. 2008;295:G403–11.

    Article  CAS  PubMed  Google Scholar 

  35. Yakabi K, Kawashima J, Kato S. Ghrelin and gastric acid secretion. World J Gastroenterol. 2008;14:6334–8.

    Article  CAS  PubMed  Google Scholar 

  36. Levin F, Edholm T, Ehrström M, Wallin B, Schmidt PT, Kirchgessner AM, et al. Effect of peripherally administered ghrelin on gastric emptying and acid secretion in the rat. Regul Pept. 2005;131:59–65.

    Article  CAS  PubMed  Google Scholar 

  37. Ogawa A, Mochiki E, Yanai M, Morita H, Toyomasu Y, Ogata K, et al. Interdigestive migrating contractions are coregulated by ghrelin and motilin in conscious dogs. Am J Physiol Regul Integr Comp Physiol. 2012;302:233–41.

    Article  Google Scholar 

  38. Fujimiya M, Ataka K, Asakawa A, Chen CY, Kato I, Inui A. Ghrelin, des-acyl ghrelin and obestatin on the gastrointestinal motility. Peptides. 2011;32:2348–51.

    Article  CAS  PubMed  Google Scholar 

  39. Ariga H, Nakade Y, Tsukamoto K, Imai K, Chen C, Mantyh C, et al. Ghrelin accelerates gastric emptying via early manifestation of antropyloric coordination in conscious rats. Regul Pept. 2008;146:112–6.

    Article  CAS  PubMed  Google Scholar 

  40. Peteers TL. Central and peripheral mechanisms by which ghrelin regulates gut motility. J Physiol Pharmacol. 2003;54:95–103.

    Google Scholar 

  41. Yang CG, Wang WG, Yan J, Fei J, Wang ZG, Zheng Q. Gastric motility in ghrelin receptor knockout mice. Mol Med Report. 2012 (Epub ahead of print).

  42. Bülbül M, Babygirija R, Zheng J, Ludwig K, Xu H, Lazar J, et al. Food intake and interdigestive gastrointestinal motility in ghrelin receptor mutant rats. J Gastroenterol. 2011;46:469–78.

    Article  PubMed  Google Scholar 

  43. Stengel A, Taché Y. Ghrelin: new insight to mechanisms and treatment of postoperative gastric ileus. Curr Pharm Des. 2011;17:1587–93.

    Article  CAS  PubMed  Google Scholar 

  44. Fujitsuka N, Asakawa A, Amitani H, Fujimiya M, Inui A. Ghrelin and gastrointestinal movement. Methods Enzymol. 2012;514:289–301.

    Article  CAS  PubMed  Google Scholar 

  45. Wren AM, Small CJ, Abbott CR, Dhillo WS, Seal LJ, Cohen MA, et al. Ghrelin causes hyperphagia and obesity in rats. Diabetes. 2001;50:2540–7.

    Article  CAS  PubMed  Google Scholar 

  46. Mondal MS, Date Y, Yamaguchi H, Toshinai K, Tsuruta T, Kangawa K, et al. Identification of ghrelin and its receptor in neurons of the rat arcuate nucleus. Regul Pept. 2005;126:55–9.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (No.30470642, No.30670780, No.31071014, No.81100260 and No.81270460); Shandong Province Tackle Key Problems in Science and Technology Program (2008GG10002006); Qingdao Municipal Science and Technology Commission (05-1-JC-93) and Shandong Province Health Department (No.2007HZ026) and the Ministry of Chinese Science and Technology Department (2006CB910505 and 11-2-3-3-(2)-nsh).

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Authors and Affiliations

  1. Department of Pathophysiology, Medical College of Qingdao University, Qingdao, 266021, Shandong, China

    Yanling Gong, Luo Xu, Feifei Guo, Zhenyan Shi, Shengli Gao & Xiangrong Sun

  2. Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, Shandong, China

    Yanling Gong

  3. Otolaryngology Department, Qingdao Municipal Hospital, Qingdao, Shandong, China

    Mingjie Pang

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  1. Yanling Gong
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Correspondence to Luo Xu.

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Gong, Y., Xu, L., Guo, F. et al. Effects of ghrelin on gastric distension sensitive neurons and gastric motility in the lateral septum and arcuate nucleus regulation. J Gastroenterol 49, 219–230 (2014). https://doi.org/10.1007/s00535-013-0789-y

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