Expression of serotonin receptors in human lower esophageal sphincter

Li,He-Fei; Liu,Jun-Feng; Zhang,Ke; Feng,Yong

doi:10.3892/etm.2014.2050

Expression of serotonin receptors in human lower esophageal sphincter

Authors:
- He-Fei Li
- Jun-Feng Liu
- Ke Zhang
- Yong Feng
View Affiliations

Affiliations: Department of Thoracic Surgery, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China
Published online on: November 4, 2014 https://doi.org/10.3892/etm.2014.2050
Pages: 49-54

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Serotonin (5-HT) is a neurotransmitter and vasoactive amine that is involved in the regulation of a large number of physiological functions. The wide variety of 5-HT-mediated functions is due to the existence of different classes of serotonergic receptors in the mammalian gastrointestinal tract and nervous system. The aim of this study was to explore the expression of multiple types of 5-HT receptor (5-HT1AR, 5-HT2AR, 5-HT3AR, 5-HT4R, 5-HT5AR, 5-HT6R and 5-HT7R) in sling and clasp fibers from the human lower esophageal sphincter (LES). Muscle strips of sling and clasp fibers from the LES were obtained from patients undergoing esophagogastrectomy, and circular muscle strips from the esophagus and stomach were used as controls. Reverse transcription‑polymerase chain reaction (RT-PCR), quantitative PCR and western blotting were used to investigate the expression of the various 5-HT receptor types. Messenger RNA for all seven 5-HT receptor types was identified in the sling and clasp fibers of the LES. At the mRNA level, the expression levels were highest for 5-HT3AR and 5-HT4R, and lowest for 5-HT5AR, 5-HT6R and 5-HT7R. At the protein level, the expression levels were highest for 5-HT3AR and 5-HT4R, followed by 5-HT1AR and 5-HT2AR; 5-HT7R was also detected at a low level. The expression of 5-HT5AR and 5-HT6R proteins was not confirmed. The results indicate that a variety of 5-HT receptor types can be detected in the human LES and probably contribute to LES function.

View Figures

View References

1	Hoyer D, Hannon JP and Martin GR: Molecular, pharmacological and functional diversity of 5-HT receptors. Pharmacol Biochem Behav. 71:533–554. 2002. View Article : Google Scholar : PubMed/NCBI
2	Beattie DT and Smith JA: Serotonin pharmacology in the gastrointestinal tract: a review. Naunyn-Schmiedebergs Arch Pharmacol. 377:181–203. 2008. View Article : Google Scholar : PubMed/NCBI
3	Li JP, Chang TM and Chey WY: Roles of 5-HT receptors in the release and action of secretin on pancreatic secretion in rats. Am J Physiol Gastrointest Liver Physiol. 280:G595–602. 2001.PubMed/NCBI
4	Martinucci I, de Bortoli N, Giacchino M, et al: Esophageal motility abnormalities in gastroesophageal reflux disease. World J Gastrointest Pharmacol Ther. 5:86–96. 2014.PubMed/NCBI
5	Liu JF, Gao LP, Wen SW, et al: Responses of human sling and clasp fibers to cholecystokinin (CKK) and gastrin through CCK receptors. J Gastroenterol Hepatol. 23:1608–1612. 2008. View Article : Google Scholar : PubMed/NCBI
6	Liu JF, Lu HL, Wen SW and Wu RF: Effects of acetylcholine on sling and clasp fibers of the human lower esophageal sphincter. J Gastroenterol Hepatol. 26:1309–1317. 2011. View Article : Google Scholar : PubMed/NCBI
7	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2 (−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar
8	Meneses A: 5-HT systems: emergent targets for memory formation and memory alterations. Rev Neurosci. 24:629–64. 2013. View Article : Google Scholar : PubMed/NCBI
9	Kato S: Role of serotonin 5-HT3 receptors in intestinal inflammation. Biol Pharm Bull. 36:1406–1409. 2013. View Article : Google Scholar
10	Hayes DJ and Greenshaw AJ: 5-HT receptors and reward-related behaviour: a review. Neurosci Biobehav Rev. 35:1419–1449. 2011. View Article : Google Scholar : PubMed/NCBI
11	Schneider JH, Küper MA, Königsrainer A and Brücher BL: Transient lower esophageal sphincter relaxation and esophageal motor response. J Surg Res. 159:714–719. 2010. View Article : Google Scholar
12	Gershon MD: Review article: serotonin receptors and transporters - roles in normal and abnormal gastrointestinal motility. Aliment Pharmacol Ther. 20:3–14. 2004. View Article : Google Scholar
13	Liu XB and Liu JF: Expression of dopamine receptors in human lower esophageal sphincter. J Gastroenterol Hepatol. 27:945–950. 2012. View Article : Google Scholar : PubMed/NCBI
14	Hansen MB and Jaffe BM: 5-HT receptor subtypes involved in luminal serotonin-induced secretion in rat intestine in vivo. J Surg Res. 56:277–287. 1994. View Article : Google Scholar : PubMed/NCBI
15	Thompson AJ and Lummis SC: The 5-HT3 receptor as a therapeutic target. Expert Opin Ther Targets. 11:527–540. 2012. View Article : Google Scholar
16	Walstab J, Rappold G and Niesler B: 5-HT (3) receptors: role in disease and target of drugs. Pharmacol Ther. 128:146–169. 2010. View Article : Google Scholar : PubMed/NCBI
17	Mader R, Kocher T, Haier J, et al: Investigation of serotonin type 4 receptor expression in human and non-human primate gastrointestinal samples. Eur J Gastroenterol Hepatol. 18:945–950. 2006. View Article : Google Scholar : PubMed/NCBI
18	Champaneria S, Costall B, Naylor RJ and Robertson DW: Identification and distribution of 5-HT3 recognition sites in the rat gastrointestinal tract. Br J Pharmacol. 106:693–696. 1992. View Article : Google Scholar : PubMed/NCBI
19	Irving HR, Tan YY, Tochon-Danguy N, et al: Comparison of 5-HT4 and 5-HT7 receptor expression and function in the circular muscle of the human colon. Life Sci. 80:1198–1205. 2007. View Article : Google Scholar : PubMed/NCBI
20	Wang GD, Wang XY, Zou F, et al: Mast cell expression of the serotonin1A receptor in guinea pig and human intestine. Am J Physiol Gastrointest Liver Physiol. 304:G855–G863. 2013. View Article : Google Scholar : PubMed/NCBI
21	Waeber C, Grailhe R, Yu XJ, Hen R and Moskowitz MA: Putative 5-ht5 receptors: localization in the mouse CNS and lack of effect in the inhibition of dural protein extravasation. Ann NY Acad Sci. 861:85–90. 1998S. View Article : Google Scholar
22	Nelson DL: 5-HT5 receptors. Curr Drug Targets CNS Neurol Disord. 3:53–58. 2004. View Article : Google Scholar : PubMed/NCBI
23	Marazziti D, Baroni S, Catena Dell’Osso M, Bordi F and Borsini F: Serotonin receptors of type 6 (5-HT6): what can we expect from them? Curr Med Chem. 18:2783–2790. 2011. View Article : Google Scholar : PubMed/NCBI
24	Bonasera SJ, Chu HM, Brennan TJ and Tecott LH: A null mutation of the serotonin 6 receptor alters acute responses to ethanol. Neuropsychopharmacology. 31:1801–1813. 2006. View Article : Google Scholar : PubMed/NCBI
25	Chiu HJ, Wang YC, Liou JH, et al: Serotonin 6 receptor polymorphism in schizophrenia: frequency, age at onset and cognitive function. Neuropsychobiology. 43:113–116. 2001. View Article : Google Scholar : PubMed/NCBI
26	Janssen P, Prins NH, Moreaux B, et al: Characterization of 5-HT7-receptor-mediated gastric relaxation in conscious dogs. Am J Physiol Gastrointest Liver Physiol. 289:108–115. 2005. View Article : Google Scholar
27	Janssen P, Prins NH, Moreaux B, et al: In vivo characterization of 5-HT1A receptor-mediated gastric relaxation in conscious dogs. Br J Pharmacol. 140:913–920. 2003. View Article : Google Scholar : PubMed/NCBI
28	Janssen P, Prins NH, Meulemans AL, et al: Smooth muscle 5-HT2A receptors mediating contraction of porcine isolated proximal stomach strips. Br J Pharmacol. 137:1217–1224. 2002. View Article : Google Scholar : PubMed/NCBI
29	Prins NH, van der Grijn A, Lefebvre RA, et al: 5-HT(4) receptors mediating enhancement of contractility in canine stomach; an in vitro and in vivo study. Br J Pharmacol. 132:1941–1947. 2001. View Article : Google Scholar : PubMed/NCBI
30	Fox A and Morton IK: An examination of the 5-HT3 receptor mediating contraction and evoked [3H]-acetylcholine release in the guinea-pig ileum. Br J Pharmacol. 101:553–558. 1990. View Article : Google Scholar : PubMed/NCBI
31	Di Stefano M, Papathanasopoulos A, Blondeau K, et al: Effect of buspirone, a 5-HT1A receptor agonist, on esophageal motility in healthy volunteers. Dis Esophagus. 25:470–476. 2012. View Article : Google Scholar
32	Cohen ML, Susemichel AD, Bloomquist W and Robertson DW: 5-HT4 receptors in rat but not guinea pig, rabbit or dog esophageal smooth muscle. Gen Pharmacol. 25:1143–1148. 1994. View Article : Google Scholar : PubMed/NCBI
33	Machu TK: Therapeutics of 5-HT3 receptor antagonists: current uses and future directions. Pharmacol Ther. 130:338–347. 2011. View Article : Google Scholar : PubMed/NCBI
34	Miyata K, Yamano M, Kamato T and Akuzawa S: Effect of serotonin (5-HT)3-receptor antagonists YM060, YM114 (KAE-393), ondansetron and granisetron on 5-HT4 receptors and gastric emptying in rodents. Jpn J Pharmacol. 69:205–214. 1995. View Article : Google Scholar : PubMed/NCBI
35	Poole DP, Xu B, Koh SL, et al: Identification of neurons that express 5-hydroxytryptamine4 receptors in intestine. Cell Tissue Res. 325:413–422. 2006. View Article : Google Scholar : PubMed/NCBI
36	Saegusa Y, Takeda H, Muto S, et al: Decreased motility of the lower esophageal sphincter in a rat model of gastroesophageal reflux disease may be mediated by reductions of serotonin and acetylcholine signaling. Biol Pharm Bull. 34:704–711. 2011. View Article : Google Scholar : PubMed/NCBI
37	Ren J, Zhou X and Galligan JJ: 5-HT4 receptor activation facilitates recovery from synaptic rundown and increases transmitter release from single varicosities of myenteric neurons. Am J Physiol Gastrointest Liver Physiol. 294:G1376–1383. 2008. View Article : Google Scholar : PubMed/NCBI
38	Taniyama K, Kaibara M, Uezono Y and Hayashi H: Functional difference of prokinetics depending on subtypes and localization of receptor in alimentary tract. Nihon Yakurigaku Zasshi. 122(Suppl): 63PP–66PP. 2003.(In Japanese).
39	Vanhoenacker P, Haegeman G and Leysen JE: 5-HT7 receptors: current knowledge and future prospects. Trends Pharmacol Sci. 21:70–77. 2000. View Article : Google Scholar : PubMed/NCBI
40	Tonini M, Vicini R, Cervio E, et al: 5-HT7 receptors modulate peristalsis and accommodation in the guinea pig ileum. Gastroenterology. 129:1557–1566. 2005. View Article : Google Scholar : PubMed/NCBI
41	Liu H, Irving HR and Coupar IM: Expression patterns of 5-HT7 receptor isoforms in the rat digestive tract. Life Sci. 69:2467–2475. 2001. View Article : Google Scholar : PubMed/NCBI
42	Yang L, Cai H, Tou J, et al: The role of the 5-hydroxytryptamine pathway in reflux-induced esophageal mucosal injury in rats. World J Surg Oncol. 10:2192012. View Article : Google Scholar : PubMed/NCBI