title: Neurotensin modulates pacemaker activity in interstitial cells of Cajal from the mouse small intestine.
abstract: Neurotensin, a tridecapeptide localized in the gut to discrete enteroendocrine cells of the small bowel mucosa, is a hormone that plays an important role in gastrointestinal secretion, growth, and motility. Neurotensin has inhibitory and excitatory effects on peristaltic activity and produces contractile and relaxant responses in intestinal smooth muscle. Our objective in this study is to investigate the effects of neurotensin in small intestinal interstitial cells of Cajal (ICC) and elucidate the mechanism. To determine the electrophysiological effects of neurotensin on ICC, whole-cell patch clamp recordings were performed in cultured ICC from the small intestine. Exposure to neurotensin depolarized the membrane of pacemaker cells and produced tonic inward pacemaker currents. Only neurotensin receptor1 was identified when RT-PCR and immunocytochemistry were performed with mRNA isolated from small intestinal ICC and c-Kit positive cells. Neurotensin-induced tonic inward pacemaker currents were blocked by external Na⁺-free solution and in the presence of flufenamic acid, an inhibitor of non-selective cation channels. Furthermore, neurotensin-induced action is blocked either by treatment with U73122, a phospholipase C inhibitor, or thapsigargin, a Ca²⁺-ATPase inhibitor in ICC. We found that neurotensin increased spontaneous intracellular Ca²⁺ oscillations as seen with fluo4/AM recording. These results suggest that neurotensin modulates pacemaker currents via the activation of non-selective cation channels by intracellular Ca²⁺-release through neurotensin receptor1.
authors.affiliation: Department of Internal Medicine, College of Medicine, Chosun University, Gwangju 501-759, Korea.
authors.forename: Jun
authors.initials: J
authors.lastname: Lee
authors.forename: Young Dae
authors.initials: YD
authors.lastname: Kim
authors.forename: Chan Guk
authors.initials: CG
authors.lastname: Park
authors.forename: Man Yoo
authors.initials: MY
authors.lastname: Kim
authors.forename: In Yeoub
authors.initials: IY
authors.lastname: Chang
authors.forename: Dong Chuan
authors.initials: DC
authors.lastname: Zuo
authors.forename: Pawan Kumar
authors.initials: PK
authors.lastname: Shahi
authors.forename: Seok
authors.initials: S
authors.lastname: Choi
authors.forename: Cheol Ho
authors.initials: CH
authors.lastname: Yeum
authors.forename: Jae Yeoul
authors.initials: JY
authors.lastname: Jun
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D056885:Interstitial Cells of Cajal / Q000187:drug effects / Q000378:metabolism*; D007421:Intestine, Small / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007473:Ion Channels / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009130:Muscle, Smooth / Q000378:metabolism*; D009496:Neurotensin / Q000378:metabolism* / Q000494:pharmacology*; D018028:Receptors, Neurotensin / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D007473:Ion Channels; D018028:Receptors, Neurotensin; C114036:neurotensin type 1 receptor; D009496:Neurotensin; D012964:Sodium; D010738:Type C Phospholipases; D000252:Calcium-Transporting ATPases; D002118:Calcium