Neurotensin Modulates Pacemaker Activity in Interstitial Cells of Cajal from the Mouse Small Intestine

• Published in: Molecules and cells 2012, 33(5), , pp.509-516
• Main Authors: Lee, J., Chosun University, Gwangju, Republic of Korea, Kim, Y.D., Chosun University, Gwangju, Republic of Korea, Park, C.G., Chosun University, Gwangju, Republic of Korea, Kim, M.Y., Chosun University, Gwangju, Republic of Korea, Chang, I.Y., Chosun University, Gwangju, Republic of Korea, Zuo, Dong Chuan, Chosun University, Gwangju, Republic of Korea, Shahi, Pawan Kumar, Chosun University, Gwangju, Republic of Korea, Choi, S., Chosun University, Gwangju, Republic of Korea, Yeum, C.H., Chosun University, Gwangju, Republic of Korea, Jun, J.Y., Chosun University, Gwangju, Republic of Korea
• Format: Article
• Language: English
• Subjects: Animals; Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Calcium - metabolism; Calcium-Transporting ATPases - antagonists & inhibitors; Calcium-Transporting ATPases - metabolism; Cell Biology; Cells, Cultured; Endoplasmic Reticulum - metabolism; Female; GASTROINTESTINAL MOTILITY; In Vitro Techniques; interstitial cells of Cajal; Interstitial Cells of Cajal - drug effects; Interstitial Cells of Cajal - metabolism; Intestine, Small - cytology; Intestine, Small - drug effects; Intestine, Small - metabolism; Ion Channels - metabolism; Life Sciences; Male; Membrane Potentials - physiology; Mice; Mice, Inbred BALB C; MOTRICITE GASTRO-INTESTINALE; MOVILIDAD GASTROINTESTINAL; Muscle, Smooth - metabolism; neurotensin; Neurotensin - metabolism; Neurotensin - pharmacology; neurotensin receptor1; Receptors, Neurotensin - metabolism; Sodium - metabolism; Type C Phospholipases - antagonists & inhibitors; Type C Phospholipases - metabolism; 생물학
• ISSN: 1016-8478; 0219-1032
• DOI: 10.1007/s10059-012-2290-5

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.