title: Spexin Enhances Bowel Movement through Activating L-type Voltage-dependent Calcium Channel via Galanin Receptor 2 in Mice.
abstract: A novel neuropeptide spexin was found to be broadly expressed in various endocrine and nervous tissues while little is known about its functions. This study investigated the role of spexin in bowel movement and the underlying mechanisms. In functional constipation (FC) patients, serum spexin levels were significantly decreased. Consistently, in starved mice, the mRNA of spexin was significantly decreased in intestine and colon. Spexin injection increased the velocity of carbon powder propulsion in small intestine and decreased the glass beads expulsion time in distal colon in mice. Further, spexin dose-dependently stimulated the intestinal/colonic smooth muscle contraction. Galanin receptor 2 (GALR2) antagonist M871, but not Galanin receptor 3 (GALR3) antagonist SNAP37899, effectively suppressed the stimulatory effects of spexin on intestinal/colonic smooth muscle contraction, which could be eliminated by extracellular [Ca(2+)] removal and L-type voltage-dependent Ca(2+) channel (VDCC) inhibitor nifedipine. Besides, spexin dramatically increased the [Ca(2+)]i in isolated colonic smooth muscle cells. These data indicate that spexin can act on GALR2 receptor to regulate bowel motility by activating L-type VDCC. Our findings provide evidence for important physiological roles of spexin in GI functions. Selective action on spexin pathway might have therapeutic effects on GI diseases with motility disorders.
authors.affiliation: 1] Lab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China [2] YMU-HKBU Joint Laboratory of Traditional Natural Medicine, Yunnan Minzu University, Kunming, China.
authors.forename: Cheng-yuan
authors.initials: CY
authors.lastname: Lin
authors.affiliation: 1] Lab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China [2] School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, China.
authors.forename: Man
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Lab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Huang
authors.affiliation: Lab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.
authors.forename: Li-ling
authors.initials: LL
authors.lastname: Yang
authors.affiliation: Lab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.
authors.forename: Hai-bo
authors.initials: HB
authors.lastname: Fu
authors.affiliation: Lab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Lab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.
authors.forename: Linda L D
authors.initials: LL
authors.lastname: Zhong
authors.affiliation: Lab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.
authors.forename: Huai-xue
authors.initials: HX
authors.lastname: Mu
authors.affiliation: Lab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.
authors.forename: Xiao-ke
authors.initials: XK
authors.lastname: Shi
authors.affiliation: Lab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.
authors.forename: Christina F P
authors.initials: CF
authors.lastname: Leung
authors.affiliation: 1] Lab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China [2] YMU-HKBU Joint Laboratory of Traditional Natural Medicine, Yunnan Minzu University, Kunming, China.
authors.forename: Bao-min
authors.initials: BM
authors.lastname: Fan
authors.affiliation: Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Lab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.
authors.forename: Ai-ping
authors.initials: AP
authors.lastname: Lu
authors.affiliation: University at Buffalo School of Medicine and Biomedical Sciences, 3435 Main Street, Buffalo, NY,USA.
authors.forename: Li-xin
authors.initials: LX
authors.lastname: Zhu
authors.affiliation: 1] Lab of Brain and Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China [2] YMU-HKBU Joint Laboratory of Traditional Natural Medicine, Yunnan Minzu University, Kunming, China.
authors.forename: Zhao-xiang
authors.initials: ZX
authors.lastname: Bian
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D016022:Case-Control Studies; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D003248:Constipation / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D005772:Gastrointestinal Transit / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D009543:Nifedipine / Q000627:therapeutic use; D036361:Peptide Hormones / Q000378:metabolism*; D010455:Peptides / Q000627:therapeutic use; D044092:Receptor, Galanin, Type 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D044093:Receptor, Galanin, Type 3 / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: C510288:1-phenyl-3-((3-(trifluoromethyl)phenyl)imino)-1H-indol-2-one; D020746:Calcium Channels, L-Type; D007211:Indoles; C000603588:M871 peptide; D009479:Neuropeptides; D036361:Peptide Hormones; D010455:Peptides; D044092:Receptor, Galanin, Type 2; D044093:Receptor, Galanin, Type 3; C546416:SPX protein, human; D009543:Nifedipine; D002118:Calcium