Prenatal gelişim boyunca koyun ileumunda kannabinoid reseptör 2’nin ekspresyon profili

Amaç: Bu çalışmada prenatal gelişim boyunca koyun ileumundaki kannabinoid reseptör 2 (CB2)’nin ekspresyonunu araştırmayı amaçladık. Gereç ve Yöntem: Çalışmamızda fötal yaşı 63 ile 147 gün arasında değişen 20 adet koyun fötüsünün ileum örnekleri kullanıldı. CB2 ekspresyonunu göstermek için Streptavidin-Biotin peroksidaz immunohistokimya yöntemini kullandık. Bulgular: Bağırsak epitelinin çoğunluğu CB2 için zayıf bir pozitif reaksiyon gösterdi. İlginç bir şekilde, hem villus hem de kriptlerin bazı epitel hücrelerinde yoğun intrasitoplazmik boyanma gözlemledik. Ayrıca, submukozal ve miyenterik pleksustaki ganglion hücrelerinde CB2 immun reaktivitesi gözlendi. Üstelik, lamina ve tunica muskularisteki düz kas hücrelerinde de pozitif boyanma tespit ettik. Prenatal dönemin sonuna doğru, histolojik olarak olgun Peyer plaklarına rastladık. Follikül ve dom bölgesini oluşturan immune sistem hücrelerinin çoğunda CB2 boyanması tespit edildi. Ayrıca, follikülle ilişkili epitelde CB2 ile pozitif boyandı. Öneri: Bu çalışma fötal koyun ileumda CB2 ekspresyonunu tanımlayan ilk çalışmadır. Fizyolojik koşullar altında, CB2 ekspresyonu fetal koyun ileumdaki epitel hücrelerinde, düz kaslarda, enterik nöronlarda ve Peyer plaklarında belirlendi. CB2 kuvvetli boyanan epitel hücrelerinin morfolojisi ve önceki araştırmacıların bulguları göz önüne alındığında, CB2 prenatal dönemde enteroendokrin hücreler için biyolojik bir belirteç olabilir.

Expression profile of cannabinoid receptor 2 in ovine ileum during prenatal development

Aim: Here, we aimed to explore cannabinoid receptor 2 (CB2) expression in ovine ileum during prenatal development using immunohistochemistry.Materials and Methods: We used 20 ileal samples from fetal sheep whose gestational ages range from 63 to 147 days. To visualize CB2 expression in ileum, we applied labeled Streptavidin Biotin method to paraffin sections.Results: The majority of the intestinal epithelium showed a weak positive reaction for CB2. Interestingly, we observed intense intracytoplasmic staining in some epithelial cells of both intestinal villi and crypts. Moreover, CB2 immunoreaction was observed in ganglion cells in submucosal and myenteric plexus. We also determined positive staining in smooth muscle cells of lamina and tunica muscularis. Towards the end of the prenatal period, we found histologically mature Peyer’s patches. CB2 staining was detected in the majority ofimmune cells forming the follicle and dome region. Follicle associated epithelium also showed CB2 immunoreaction.Conclusion: The present study is the first to describe CB2 expression in fetal sheep ileum. CB2 expression was determined in epithelial cells, smooth muscles, enteric neurons and Peyer’s patches in ileum fetal sheep under physiological conditions. Considering the morphology of epithelial cells with intense CB2 staining and previous findings, CB2 may be a possible marker for enteroendocrine cells during the prenatal period.

___

  • Abalo R, Rivera AJ, Vera G, Suardíaz M, et al., 2005. Evaluation of the effect of age on cannabinoid receptor functionality and expression in guinea-pig ileum longitudinal musclemyenteric plexus preparations. Neurosci Lett, 383(1-2), 176-181.
  • Alhouayek M, Muccioli GG, 2012. The endocannabinoid system in inflammatory bowel diseases: from pathophysiology to therapeutic opportunity. Trends Mol Med, 18(10), 615-625.
  • Camus S, Ko WKD, Pioli E, Bezard E, 2015. Why bother using non-human primate models of cognitive disorders in translational research?. Neurobiol Learn Mem, 124, 123- 129.
  • Capasso R, Borrelli F, Aviello G, Romano B, et al., 2008. Cannabidiol, extracted from Cannabis sativa, selectively inhibits inflammatory hypermotility in mice. Br J Pharmacol, 154(5), 1001-1008.
  • Casal M, Haskins M, 2006. Large animal models and gene therapy. Eur J Hum Genet, 14(3), 266-272.
  • Comar KM, Kirby DF, 2005. Herbal remedies in gastroenterology. J Clin Gastroenterol, 39(6), 457-468.
  • Devane WA, Hanus L, Breuer A, Pertwee RG, et al., 1992. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science, 258, 1946-1949.
  • Di Carlo G, Izzo AA, 2003. Cannabinoids for gastrointestinal diseases: potential therapeutic applications. Expert Opin Investig Drugs, 12(1), 39-49.
  • Di Marzo V, Fontana A, 1995. Anandamide, an endogenous cannabinomimetic eicosanoid: ‘killing two birds with one stone’. Prostaglandins Leukot Essent Fatty Acids, 53(1), 1-11.
  • Duncan M, Davison JS, Sharkey KA, 2005. Endocannabinoids and their receptors in the enteric nervous system. Aliment Pharmacol Ther, 22(8), 667-683.
  • Duncan M, Mouihate A, Mackie K, Keenan CM, et al., 2008. Cannabinoid CB2 receptors in the enteric nervous system modulate gastrointestinal contractility in lipopolysaccharide- treated rats. Am J Physiol Gastrointest Liver Physiol, 295(1), G78–G87.
  • Galiègue S, Mary S, Marchand J, Dussossoy D, et al., 1995. Expression of central and peripheral cannabinoid recep- tors in human immune tissues and leukocyte subpopulations. Eur J Biochem, 232(1), 54-61.
  • Gaoni Y, Mechoulam R, 1964. Isolation, structure, and partial synthesis of an active constituent of hashish. J Am Chem Soc, 86(8), 1646-1647.
  • Gribble FM, Reimann F, 2019. Function and mechanisms of enteroendocrine cells and gut hormones in metabolism. Nat Rev Endocrinol, 15(4), 226-237.
  • Grill M, Hasenoehrl C, Kienzl M, Kargl J, et al., 2019. Cellular localization and regulation of receptors and enzymes of the endocannabinoid system in intestinal and systemic inflammation. Histochem Cell Biol, 151(1), 5–20.
  • Hasenoehrl C, Taschler U, Storr M, Schicho R, 2016. The gastrointestinal tract–a central organ of cannabinoid signaling in health and disease. Neurogastroenterol Motil, 28(12), 1765-1780.
  • Hinds NM, Ullrich K, Smid SD, 2006. Cannabinoid 1 (CB1) receptors coupled tocholinergic motorneurons inhibit neurogenic circular muscle contractility in the human colon. Br J Pharmacol, 148(2), 191-199.
  • Ihenetu K, Molleman A, Parsons ME, Whelan CJ, 2003. Inhibition of interleukin-8 release in the human colonic epithelial cell line HT-29 by cannabinoids. Eur J Pharmacol, 458(1-2), 207-215.
  • Izzo AA, 2007. The cannabinoid CB2 receptor: a good friend in the gut. Neurogastroenterol Motil, 19(9), 704-708.
  • Izzo AA, 2009. Camilleri M. Cannabinoids in intestinal inflammation and cancer. Pharmacol Res, 60(2), 117-125.
  • Izzo AA, Sharkey KA, 2010. Cannabinoids and the gut: new developments and emerging concepts. Pharmacol Ther, 126(1), 21-38
  • Ligresti A, Bisogno T, Matias I, De Petrocellis L, et al., 2003. Possible endocannabinoid control of colorectal cancer growth. Gastroenterology, 125(3), 677-687.
  • Maccarrone M, Bab I, Bíró T, Cabral GA, et al., 2015, Endocannabinoid signaling at the periphery: 50 years after THC. Trends Pharmacol Sci, 36(5), 277-296.
  • Manara L, Croci T, Guagnini F, Rinaldi-Carmona M, et al., 2002. Functional assessment of neuronal cannabinoid receptors in the muscular layers of human ileum and colon. Dig Liver Dis, 34(4), 262-269.
  • Mathison R, Ho W, Pittman QJ, Davison JS, et al., 2004. Effects of cannabinoid receptor‐2 activation on accelerated gastrointestinal transit in lipopolysaccharide‐treated rats. Br J Pharmacol, 142(8), 1247-1254.
  • Matias I, Di Marzo V, 2007. Endocannabinoids and the control of energy balance. Trends Endocrinol Metab, 18(1), 27-37.
  • Moran-Ramos S, Tovar AR, Torres N, 2012. Diet: friend or foe of enteroendocrine cells: how it interacts with enteroendocrine cells. Adv Nutr, 3(1), 8-20.
  • Moss CE, Marsh WJ, Parker HE, Ogunnowo-Bada E, et al., 2012. Somatostatin receptor 5 and cannabinoid receptor 1 activation inhibit secretion of glucose-dependent insulinotropic polypeptide from intestinal K cells in rodents. Diabetologia, 55(11), 3094-3103.
  • Mulè F, Amato A, Baldassano S, Serio R, 2007. Involvement of CB1 and CB2 receptors in the modulation of cholinergic neurotransmission in mouse gastricreparations. Pharmacol Res, 56(3), 185-192.
  • Navarro G, Morales P, Rodríguez-Cueto C, Fernández-Ruiz J, et al., 2016. Targeting cannabinoid CB2 receptors in the central nervous system. Medicinal chemistry approaches with focus on neurodegenerative disorders. Front Neurosci, 10, 406.
  • Özbek M, Bayraktaroğlu AG, 2019. Developmental study on the ileal Peyer’s patches of sheep, and cytokeratin-18 as a possible marker for M cells in follicle associated epithelium. Acta Histochem, 121(3), 311-322.
  • Öztop M, Özbek M, Liman N, Beyaz F, et al., 2019. Localization profiles of natriuretic peptides in hearts of pre-hibernating and hibernating Anatolian ground squirrels (Spermophilus xanthoprymnus). Vet Res Commun, 43(2), 45-65.
  • Pesce M, D'Alessandro A, Borrelli O, Gigli S, et al., 2018. Endocannabinoid‐ related compounds in gastrointestinal diseases. J Cell Mol Med, 22(2), 706-715.
  • Petrocellis LD, Cascio MG, Marzo VD, 2004. The endocannabinoid system: a general view and latest additions. Br J Pharmacol, 141(5), 765-774.
  • Richardson C, Hebert CN, Terlecki S, 1976. Estimation of the developmental age of the ovine fetus and lamb. Vet Rec, 99(2), 22-26.
  • Sternini C, Anselmi L, Rozengurt E, 2008. Enteroendocrine, cells: a site of ‘taste’ in gastro-intestinal chemosensing. Curr Opin Endocrinol Diabetes Obes, 15(1), 73-78.
  • Storr M, Gaffal E, Saur D, Schusdziarra V, et al., 2002. Effect of cannabinoids on neural transmission in rat gastric fundus. Can J Physiol Pharmacol, 80(1), 67-76.
  • Sturm A, Dignass AU, 2008. Epithelial restitution andwound healing in inflammatory bowel disease. World J Gastroenterol, 14, 348-353.
  • Sugiura T, Kondo S, Sukagawa A, Nakane S, et al., 1995. 2-Arachidonoylgylcerol: a possible endogenous cannabinoid receptor ligand in brain. Biochem Biophys Res Commun, 215(1), 89-97.
  • Wilke M, Buijs-Offerman RM, Aarbiou J, Colledge WH, et al., 2011. Mouse models of cystic fibrosis: phenotypic analysis and research applications. J Cyst Fibros, 10, S152–S171.
  • Wright K, Rooney N, Feeney M, Tate J, et al., 2005. Differential expression of cannabinoid receptors in the human colon: cannabinoids promote epithelial wound healing. Gastroenterology, 129, 437-453.
  • Wright KL, Duncan M, Sharkey KA, 2008. Cannabinoid CB2 receptors in the gastrointestinal tract: a regulatory system in states of inflammation. Br J Pharmacol, 153(2), 263-270.
  • Yasuda M, Jenne CN, Kennedy LJ, Reynolds JD, 2006. The sheep and cattle Peyer’s patch as a site of B-cell development. Vet Res, 37, 401-415.
Eurasian Journal of Veterinary Sciences-Cover
  • ISSN: 1309-6958
  • Yayın Aralığı: Yılda 4 Sayı
  • Yayıncı: Selçuk Üniversitesi Veteriner Fakültesi