Effects of Prunus mume Siebold & Zucc. in the pacemaking activity of interstitial cells of Cajal in murine small intestine

Lee,Sang Weon; Kim,Sung Jin; Kim,Hyungwoo; Yang,Dongki; Kim,Hyun Jung; Kim,Byung Joo

doi:10.3892/etm.2016.3963

Effects of Prunus mume Siebold & Zucc. in the pacemaking activity of interstitial cells of Cajal in murine small intestine

Authors:
- Sang Weon Lee
- Sung Jin Kim
- Hyungwoo Kim
- Dongki Yang
- Hyun Jung Kim
- Byung Joo Kim
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Affiliations: Department of Neurosurgery, Pusan National University Yangsan Hospital, Yangsan, Gyeongsangnam 50612, Republic of Korea, Division of Pharmacology, Pusan National University School of Korean Medicine, Yangsan, Gyeongsangnam 50612, Republic of Korea, Department of Physiology, Gachon University College of Medicine, Incheon, Gyeonggi 22332, Republic of Korea, Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine, Yangsan, Gyeongsangnam 50612, Republic of Korea
Published online on: December 7, 2016 https://doi.org/10.3892/etm.2016.3963
Pages: 327-334

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Abstract

Interstitial cells of Cajal (ICCs) function as pacemaker cells in the gastrointestinal (GI) tract and therefore, serve an important role in regulating GI motility. The effects of a species of plum (Prunus mume Siebold & Zucc.) on cultured ICC cluster‑induced pacemaker potentials in the mouse small intestine were investigated, and the effects of a methanolic extract of Prunus mume (m‑PM) on ICC pacemaker activities were examined using the whole‑cell patch‑clamp technique. ICC pacemaker membrane potentials were depolarized by m‑PM in a concentration dependent manner in current clamp mode. 4‑Diphenylacetoxy‑N‑methyl‑piperidine methiodide, which is a muscarinic 3 (M3) receptor antagonist, was able to block m‑PM‑induced pacemaker potential increases, whereas methoctramine, which is a muscarinic 2 (M2) receptor antagonist, was not. When 1 mM guanosine diphosphate β‑5 was present in the pipette solution, m‑PM induced slight pacemaker depolarization. Following pretreatment in bath solution of Ca2+‑free solution or a Ca2+‑ATPase inhibitor in endoplasmic reticulum, the pacemaker currents were inhibited. Furthermore, pretreatment with PD98059, SB203580 or SP600125, which is a c‑jun NH2‑terminal kinase inhibitor, blocked m‑PM‑induced ICC potential depolarization. Furthermore, m‑PM inhibited transient receptor potential melastatin (TRPM) 7 channels, but did not affect Ca2+‑activated Cl‑ channels. These results suggest that m‑PM is able to modulate pacemaker potentials through the muscarinic M3 receptor, via G‑protein and external and internal Ca2+, in a mitogen‑activated protein kinase and TRPM7‑dependent manner. Therefore, m‑PM may provide a basis for the development of a novel gastroprokinetic agent.

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1	Jeong JT, Moon JH, Park KH and Shin CS: Isolation and characterization of a new compound from Prunus mume fruit that inhibits cancer cells. J Agric Food Chem. 54:2123–2128. 2006. View Article : Google Scholar : PubMed/NCBI
2	Kita M, Kato M, Ban Y, Honda C, Yaegaki H, Ikoma Y and Moriguchi T: Carotenoid accumulation in Japanese apricot (Prunus mume Siebold & Zucc.): Molecular analysis of carotenogenic gene expression and ethylene regulation. J Agric Food Chem. 55:3414–3420. 2007. View Article : Google Scholar : PubMed/NCBI
3	Kim BJ, Kim JH, Kim HP and Heo MY: Biological screening of 100 plant extracts for cosmetic use (II): Anti-oxidative activity and free radical scavenging activity. Int J Cosmet Sci. 19:299–307. 1997. View Article : Google Scholar : PubMed/NCBI
4	Tsai CH, Chang RC, Chiou JF and Liu TZ: Improved superoxide-generating system suitable for the assessment of the superoxide-scavenging ability of aqueous extracts of food constituents using ultraweak chemiluminescence. J Agric Food Chem. 51:58–62. 2003. View Article : Google Scholar : PubMed/NCBI
5	Matsuda H, Morikawa T, Ishiwada T, Managi H, Kagawa M, Higashi Y and Yoshikawa M: Medicinal flowers. VIII. Radical scavenging constituents from the flowers of Prunus mume: Structure of prunose III. Chem Pharm Bull (Tokyo). 51:440–443. 2003. View Article : Google Scholar : PubMed/NCBI
6	Kim TK, Cha MR, Kim SJ, Kim SY, Jeon KI, Park HR, Park EJ and Lee SC: Antioxidative activity of methanol extract from Prunus mume byproduct. Cancer Prev Res. 10:251–256. 2005.
7	Wang L, Zhang HY and Wang L: Comparison of pharmacological effects of Fructus Mume and its processed products. Zhong Yao Cai. 33:353–356. 2010.(In Chinese). PubMed/NCBI
8	Chen Y, Wong RW, Seneviratne CJ, Hägg U, McGrath C, Samaranayake LP and Kao R: The antimicrobial efficacy of Fructus mume extract on orthodontic bracket: A monospecies-biofilm model study in vitro. Arch Oral Biol. 56:16–21. 2011. View Article : Google Scholar : PubMed/NCBI
9	Seneviratne CJ, Wong RW, Hägg U, Chen Y, Herath TD, Samaranayake PL and Kao R: Prunus mume extract exhibits antimicrobial activity against pathogenic oral bacteria. Int J Paediatr Dent. 21:299–305. 2011. View Article : Google Scholar : PubMed/NCBI
10	Enomoto S, Yanaoka K, Utsunomiya H, Niwa T, Inada K, Deguchi H, Ueda K, Mukoubayashi C, Inoue I, Maekita T, et al: Inhibitory effects of Japanese apricot (Prunus mume Siebold et Zucc.; Ume) on Helicobacter pylori-related chronic gastritis. Eur J Clin Nutr. 64:714–719. 2010. View Article : Google Scholar : PubMed/NCBI
11	Kawahara K, Hashiguchi T, Masuda K, Saniabadi AR, Kikuchi K, Tancharoen S, Ito T, Miura N, Morimoto Y, Biswas KK, et al: Mechanism of HMGB1 release inhibition from RAW264.7 cells by oleanolic acid in Prunus mume Sieb. et Zucc. Int J Mol Med. 23:615–620. 2009.PubMed/NCBI
12	Mori S, Sawada T, Okada T, Ohsawa T, Adachi M and Keiichi K: New anti-proliferative agent, MK615, from Japanese apricot ‘Prunus mume’ induces striking autophagy in colon cancer cells in vitro. World J Gastroenterol. 13:6512–6517. 2007. View Article : Google Scholar : PubMed/NCBI
13	Kai H, Akamatsu E, Torii E, Kodama H, Yukizaki C, Sakakibara Y, Suiko M, Morishita K, Kataoka H and Matsuno K: Inhibition of proliferation by agricultural plant extracts in seven human adult T-cell leukaemia (ATL)-related cell lines. J Nat Med. 65:651–655. 2011. View Article : Google Scholar : PubMed/NCBI
14	Kim S, Park SH, Lee HN and Park T: Prunus mume extract ameliorates exercise-induced fatigue in trained rats. J Med Food. 11:460–468. 2008. View Article : Google Scholar : PubMed/NCBI
15	Youn YN, Lim E, Lee N, Kim YS, Koo MS and Choi SY: Screening of Korean medicinal plants for possible osteoclastogenesis effects in vitro. Genes Nutr. 2:375–380. 2008. View Article : Google Scholar : PubMed/NCBI
16	Chuda Y, Ono H, Ohnishi-Kameyama M, Matsumoto K, Nagata T and Kikuchi Y: Mumefural, citric acid derivative improving blood fluidity from fruit-juice concentrate of Japanese apricot (Prunus mume Sieb. et Zucc). J Agric Food Chem. 47:828–831. 1999. View Article : Google Scholar : PubMed/NCBI
17	Jung BG, Cho SJ, Koh HB, Han DU and Lee BJ: Fermented Maesil (Prunus mume) with probiotics inhibits development of atopic dermatitis-like skin lesions in NC/Nga mice. Vet Dermatol. 21:184–191. 2010. View Article : Google Scholar : PubMed/NCBI
18	Jung BG, Ko JH, Cho SJ, Koh HB, Yoon SR, Han DU and Lee BJ: Immune-enhancing effect of fermented Maesil (Prunus mume Siebold & Zucc.) with probiotics against Bordetella bronchi septica in mice. J Vet Med Sci. 72:1195–1202. 2010. View Article : Google Scholar : PubMed/NCBI
19	Huizinga JD, Thuneberg L, Kluppel M, Malysz J, Mikkelsen HB and Bernstein A: W/kit gene required for interstitial cells of Cajal and for intestinal pacemaker activity. Nature. 373:347–349. 1995. View Article : Google Scholar : PubMed/NCBI
20	Sanders KM: A case for interstitial cells of Cajal as pacemakers and mediators of neurotransmission in the gastrointestinal tract. Gastroenterology. 111:492–515. 1996. View Article : Google Scholar : PubMed/NCBI
21	Kim BJ, Lim HH, Yang DK, Jun JY, Chang IY, Park CS, So I, Stanfield PR and Kim KW: Melastatin-type transient receptor potential channel 7 is required for intestinal pacemaking activity. Gastroenterology. 129:1504–1517. 2005. View Article : Google Scholar : PubMed/NCBI
22	Lee JH, Kim SY, Kwon YK, Kim BJ and So I: Characteristics of the cholecystokinin-induced depolarization of pacemaking activity in cultured interstitial cells of Cajal from murine small intestine. Cell Physiol Biochem. 31:542–554. 2013. View Article : Google Scholar : PubMed/NCBI
23	Kim BJ, Kim SY, Lee S, Jeon JH, Matsui H, Kwon YK, Kim SJ and So I: The role of transient receptor potential channel blockers in human gastric cancer cell viability. Can J Physiol Pharmacol. 90:175–186. 2012. View Article : Google Scholar : PubMed/NCBI
24	Kim BJ, Kim HW, Lee GS, Choi S, Jun JY, So I and Kim SJ: Poncirus trifoliate fruit modulates pacemaker activity in interstitial cells of Cajal from the murine small intestine. J Ethnopharmacol. 149:668–675. 2013. View Article : Google Scholar : PubMed/NCBI
25	Koh SD, Jun JY, Kim TW and Sanders KM: A Ca²⁺-inhibited non-selective cation conductance contributes to pacemaker currents in mouse interstitial cell of Cajal. J Physiol. 540:803–814. 2002. View Article : Google Scholar : PubMed/NCBI
26	Kim BJ, So I and Kim KW: The relationship of TRP channels to the pacemaker activity of interstitial cells of Cajal in the gastrointestinal tract. J Smooth Muscle Res. 42:1–7. 2006. View Article : Google Scholar : PubMed/NCBI
27	Huizinga JD, Zhu Y, Ye J and Molleman A: High-conductance chloride channels generate pacemaker currents in interstitial cells of Cajal. Gastroenterology. 123:1627–1636. 2002. View Article : Google Scholar : PubMed/NCBI
28	Hwang SJ, Blair PJ, Britton FC, O'Driscoll KE, Hennig G, Bayguinov YR, Rock JR, Harfe BD, Sanders KM and Ward SM: Expression of anoctamin 1/TMEM16A by interstitial cells of Cajal is fundamental for slow wave activity in gastrointestinal muscles. J Physiol. 587:4887–4904. 2009. View Article : Google Scholar : PubMed/NCBI
29	Zhu MH, Kim TW, Ro S, Yan W, Ward SM, Koh SD and Sanders KM: A Ca²⁺-activated Cl(−) conductance in interstitial cells of Cajal linked to slow wave currents and pacemaker activity. J Physiol. 587:4905–4918. 2009. View Article : Google Scholar : PubMed/NCBI
30	Na JR, Oh KN, Park SU, Bae D, Choi EJ, Jung MA, Choi CY, Lee DW, Jun W, Lee KY, et al: The laxative effects of Maesil (Prunus mume Siebold & Zucc.) on constipation induced by a low-fibre diet in a rat model. Int J Food Sci Nutr. 64:333–345. 2013. View Article : Google Scholar : PubMed/NCBI
31	National Research Council, . Guide for the Care and Use of Laboratory Animals. National Academies Press (US); Washington (DC): 2011, PubMed/NCBI
32	Huizinga JD, Chang G, Diamant NE and El-Sharkawy TY: Electrophysiological basis of excitation of canine colonic circular muscle by cholinergic agents and substance P. J Pharmacol Exp Ther. 231:692–699. 1984.PubMed/NCBI
33	Inoue R and Chen S: Physiology of muscarinic receptor operated nonselective cation channels in guinea-pig ilieal smooth muscle. EXS. 66:261–268. 1993.PubMed/NCBI
34	Epperson A, Hatton WJ, Callaghan B, Doherty P, Walker RL, Sanders KM, Ward SM and Horowitz B: Molecular markers expressed in cultured and freshly isolated interstitial cells of Cajal. Am J Physiol Cell Physiol. 279:C529–C539. 2000.PubMed/NCBI
35	Komori S, Kawai M, Takewaki T and Ohashi H: GTP-binding protein involvement in membrane currents evoked by carbachol and histamine in guinea-pig ileal muscle. J Physiol. 450:105–126. 1992. View Article : Google Scholar : PubMed/NCBI
36	Ogata R, Inoue Y, Nakano H, Ito Y and Kitamura K: Oestradiol-induced relaxation of rabbit basilar artery by inhibition of voltage-dependent Ca channels through GTP-binding protein. Br J Pharmacol. 117:351–359. 1996. View Article : Google Scholar : PubMed/NCBI
37	Ward SM, Ordog T, Koh SD, Baker SA, Jun JY, Amberg G, Monaghan K and Sanders KM: Pacemaking in interstitial cells of Cajal depends upon calcium handling by endoplasmic reticulum and mitochondria. J Physiol. 525:2355–361. 2000. View Article : Google Scholar : PubMed/NCBI
38	Yagle K, Lu H, Guizzetti M, Möller T and Costa LG: Activation of mitogen-activated protein kinase by muscarinic receptors in astroglial cells: Role in DNA synthesis and effect of ethanol. Glia. 35:111–120. 2001. View Article : Google Scholar : PubMed/NCBI
39	Sakai H, Otogoto S, Chiba Y, Abe K and Misawa M: Involvement of p42/44 MAPK and RhoA protein in augmentation of ACh-induced bronchial smooth muscle contraction by TNF-alpha in rats. J Appl Physiol (1985). 97:2154–2159. 2004. View Article : Google Scholar : PubMed/NCBI
40	Nam JH, Kim WK and Kim BJ: Sphingosine and FTY720 modulate pacemaking activity in interstitial cells of Cajal from mouse small intestine. Mol Cells. 36:235–244. 2013. View Article : Google Scholar : PubMed/NCBI
41	Kim BJ, Nam JH, Kim KH, Joo M, Ha TS, Weon KY, Choi S, Jun JY, Park EJ and Wie J: Characteristics of gintonin-mediated membrane depolarization of pacemaker activity in cultured interstitial cells of Cajal. Cell Physiol Biochem. 34:873–890. 2014. View Article : Google Scholar : PubMed/NCBI
42	Kim BJ, Kim H, Lee GS, So I and Kim SJ: Effects of San-Huang-Xie-Xin-tang, a traditional Chinese prescription for clearing away heat and toxin, on the pacemaker activities of interstitial cells of Cajal from the murine small intestine. J Ethnopharmacol. 155:744–752. 2014. View Article : Google Scholar : PubMed/NCBI
43	Ahn TS, Kim DG, Hong NR, Park HS, Kim H, Ha KT, Jeon JH, So I and Kim BJ: Effects of Schisandra chinensis extract on gastrointestinal motility in mice. J Ethnopharmacol. 169:163–169. 2015. View Article : Google Scholar : PubMed/NCBI
44	Garrington TP and Johnson GL: Organization and regulation of mitogen-activated protein kinase signaling pathways. Curr Opin Cell Biol. 11:211–218. 1999. View Article : Google Scholar : PubMed/NCBI
45	Derkinderen P, Enslen H and Girault JA: The ERK/MAP-kinases cascade in the nervous system. Neuroreport. 10:R24–R34. 1999.PubMed/NCBI
46	Lukacs NW, Strieter RM, Chensue SW, Widmer M and Kunkel SL: TNF-alpha mediates recruitment of neutrophils and eosinophils during airway inflammation. J Immunol. 154:5411–5417. 1995.PubMed/NCBI
47	Nathanson NM: A multiplicity of muscarinic mechanisms: Enough signaling pathways to take your breath away. Proc Natl Acad Sci USA. 97:6245–6247. 2000. View Article : Google Scholar : PubMed/NCBI
48	Slack BE: The M3 muscarinic acetylcholine receptor is coupled to mitogen-activated protein kinase via protein kinase C and epidermal growth factor receptor kinase. Biochem J. 348:2381–387. 2000. View Article : Google Scholar : PubMed/NCBI
49	Yagle K, Lu H, Guizzetti M, Möller T and Costa LG: Activation of mitogen-activated protein kinase by muscarinic receptors in astroglial cells: Role in DNA synthesis and effect of ethanol. Glia. 35:111–120. 2001. View Article : Google Scholar : PubMed/NCBI