• Korean Journal of Veterinary Research
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• v.33 no.3
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• pp.361-368
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• 1993

The midbrain periaqueductal gray is a midline structure that encircles the mesencephalic aqueduct of midbrain and plays an important role in anaglgesia and modulation of nociceptive input to the central nervous system. It has been demonstrated that the periaqueductal gray contains several neuropeptides including neurotensin, which has been postulated antinociceptive effect to the periaqueductal gray. The present study was performed to provide immunohistochemical localization of neurotensin of midbrain periaqueductal gray in the Korean native goat by using immunohistochemical method. Neurotensin-like immunireactive neurons were localized throughout the midbrain periaqueductal gray, although more immunoreactive neurons were present in the middle and caudal parts of periaquductal gray than the rostral part. Dense neurotensin-like immunoreactive neurons were much more numerous in the ventral lateral division of the mid- and caudal periaqueductal grays. Neurotensin-like immunoreactive neurons were much larger and more prominent near the external margin of the gray than in the juxta-aqueductal region. Neurotensin-like immunoreactive fibers were observed as short processes extending from immunoreactive cells and some small immunoreactive puncta and varicose-like fibers were also seen.

• Korean Journal of Veterinary Research
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• v.39 no.1
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• pp.20-26
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• 1999

To investigate the regional distribution and relative frequency of the neurotensin-, pancreatic polypeptide(PP)- and gastrin/cholecystokinin(Gas/CCK)-immunoreactive cells in the gastrointestinal tract of the bullfrog(Rana catesbeiana) with developmental stages, group of bullfrogs subdivided into the tadpole with hindlegs, metamorphosed bullfrog with tail, 2 weeks after metamorphosed bullfrog and adult bullfrog, were stained by immunohistochemical methods (PAP methods). Neurotensin-immunoreactive cells were observed from the pylorus of the metamorphosed bullfrog with tail, but these cells were not detected after that periods. PP-immunoreactive cells were detected from the adult bullfrog in the pylorus, duodenum and ileum. These cells were most predominant in the pylorus. Gas/CCK-immunoreactive cells were observed from the adult bullfrog in the pylorus. According to these results, most of immunoreactive cells in the gastrointestinal tract of the bullfrog were appeared after the complete metamorphosed periods, in which the complete differentiation of structure of gastrointestinal tract were occurred, and variable changes of the regional distribution and relative frequency with developmental stages were observed.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.6
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• pp.495-501
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• 2001

We have cloned the mouse neurotensin/neuromedin N (NT/N) gene from the murine mast cell line Cl.MC/C57.1 for the first time. The murine NT/N cDNA clone consisted of 765 nucleotides and coded for 169 peptide residues with an N-terminal signal peptide, and the C-terminal region contained of one copy of neurotensin (NT) and one copy of neuromedin N (NN). Total of four Lys-Arg dibasic motifs were present; one each at the middle of the open reading frame, at the N-terminal of NN, at the C-terminal of NT, and between NN and NT. Amino acid sequence analysis of the mouse NT/N revealed 90% homology to that of the rat NT/N gene. NT/N is expressed in murine mast cell lines (Cl.MC/C57.1 and P815), but not in murine bone marrow-derived mast cells (BMMCs), murine macrophage cell line (RAW 264.7), nor in murine T cell line (EL-4). NT/N mRNA in C1.MC/C57.1 is highly inducible by IgE cross-linking, phorbol myristate acetate, neurotensin, and substance P. Following the treatment of demethylating agent, 5-azacytidine (5-azaC), the NT/N gene was induced in BMMCs in response to IgE cross-linking. 5-azaC-treated BMMCs did not express the NT/N gene without additional stimuli. These findings suggested that the regulation of NT/N gene expression was dependent on the effects of not only gene methylation but also enhancer and/or repressor proteins acting on the NT/N promoter.

• Proceedings of the Korean Biophysical Society Conference
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• 1998.06a
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• pp.32-32
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• 1998

The effect of neurotensin (NT) was investigated in rat pheochromocytoma (PC12) cells. When PC12 cells were treated with micromolar concentrations of NT, [$^3$H]norepinephrine ([$^3$H]NE) secretion and elevation of cytosolic Ca$\^$2＋/ concentration ([Ca$\^$2＋/]i) were evoked in a concentration-dependent manner with an EC$\sub$50/ of 50 ${\mu}$M.(omitted)

• Molecules and Cells
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• v.41 no.6
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• pp.591-602
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• 2018

Gastric cancer is the fifth most common type of malignancy worldwide, and the survival rate of patients with advanced-stage gastric cancer is low, even after receiving chemotherapy. Here, we validated neurotensin receptor 1 (NTSR1) as a potential therapeutic target in gastric cancer. We compared NTSR1 expression levels in sixty different gastric cancer-tissue samples and cells, as well as in other cancer cells (lung, breast, pancreatic, and colon), by assessing NTSR1 expression via semi-quantitative real-time reverse transcription polymerase chain reaction, immunocytochemistry and western blot. Following neurotensin (NT) treatment, we analyzed the expression and activity of matrix metalloproteinase-9 (MMP-9) and further determined the effects on cell migration and invasion via wound-healing and transwell assays. Our results revealed that NTSR1 mRNA levels were higher in gastric cancer tissues than non-cancerous tissues. Both of NTSR1 mRNA levels and expression were higher in gastric cancer cell lines relative to levels observed in other cancer-cell lines. Moreover, NT treatment induced MMP-9 expression and activity in all cancer cell lines, which was significantly decreased following treatment with the NTSR1 antagonist SR48692 or small-interfering RNA targeting NTSR1. Furthermore, NT-mediated metastases was confirmed by observing epithelial-mesenchymal transition markers SNAIL and E-cadherin in gastric cancer cells. NT-mediated invasion and migration of gastric cancer cells were reduced by NTSR1 depletion through the Erk signaling. These findings strongly suggested that NTR1 constitutes a potential therapeutic target for the inhibition of gastric cancer invasion and metastasis.

• Korean Journal of Veterinary Research
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• v.28 no.2
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• pp.251-259
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• 1988

Regional distribution and relative frequency of endocrine cells in ten portions of the gastrointestinal tract of the Korean native cattle were observed by immunocytochemical methods using specific antisera against chromogranin, serotonin, somatostatin, glucagon, bovine pancreatic polypeptide(BPP), motilin, gastric inhibitory polypeptide(GIP), neurotensin, secretin, gastrin and substance P. The results observed are summarized as follows: In the abomasum, chromogranin-, serotonin-, somatostatin-, motilin-, glucagon-, gastrin-, and substance P-immunoreactive cells were found. Chromogranin-and serotonin-immunoreactive cells were more numerous in the fundic region than pyloric region. Somatostatin- and gastrinimmunoreactive cells were numerous in the pyloric region than in the fundic region. In the small intestine, chromogranin-, serotonin-, somatostatin-, glucagon-, BPP-, motilin-, gastrin-, GIP-, neurotensin-, secretin-, and substance P-immunoreactive cells were detected. Chromogranin-, somatostatin-, GIP- and secretin-immunoreactive cells were most numerous in the duodenum, while BPP-, motilin-, glucagon-, neurotensin- and substance P-immunoreactive cells were rarely seen in the small intestine. In the large intestine, chromogranin-, serotonin- and BPP-immunoreactive cells were widely distributed and most numerous in the rectum. Somatostatin-, glucagon- and substance P-immunoreactive cells were rarely seen in the large intestine.

• Korean Journal of Veterinary Research
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• v.37 no.1
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• pp.9-13
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• 1997

The gastrointestinal endocrine cells of the African clawed toad, Xenopus laevis have been investigated immunohistochemically using the avidin-biotin method. Seven antisera were tested and three endocrine cell types immunoreacted with antisera to neurotensin, GRP and substance P. A moderate number of neurotensin-immunoreactive cells were weakly reacted in the small intestine. GRP-immunoreactive cells were mainly situated among the upper portion in the fundic glands, and the basal portion in the pyloric glands. These cells were oval and round in shape. On the other hand, in the intestine they were thin spindly cells with the epithelium. Substance P-immunoreactive cells were observed in among intestinal epithelium. However, no secretin-, motilin-, M-Enk- and PYY-immunoreactive cells were found in the GIT of the African clawed toads.

• The Korean Journal of Pain
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• v.33 no.4
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• pp.318-325
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• 2020

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a major side effect of anti-cancer drugs. Neurotensin receptors (NTSRs) are widely distributed within the pain circuits in the central nervous system. The purpose of this study was to determine the role of NTSR1 by examining the effects of an NTSR1 agonist in rats with CIPN and investigate the contribution of spinal serotonin receptors to the antinociceptive effect. Methods: Sprague-Dawley rats (weight 150-180 g) were used in this study. CIPN was induced by injecting cisplatin (2 mg/kg) once a day for 4 days. Intrathecal catheters were placed into the subarachnoid space of the CIPN rats. The antiallodynic effects of intrathecally or intraperitoneally administered PD 149163, an NTSR1 agonist, were evaluated. Furthermore, the levels of serotonin in the spinal cord were measured by high-performance liquid chromatography. Results: Intrathecal or intraperitoneal PD 149163 increased the paw withdrawal threshold in CIPN rats. Intrathecal administration of the NTSR1 antagonist SR 48692 suppressed the antinociceptive effect of PD 149163 given via the intrathecal route, but not the antinociceptive effect of intraperitoneally administered PD 149163. Intrathecal administration of dihydroergocristine, a serotonin receptor antagonist, suppressed the antinociceptive effect of intrathecally administered, but not intraperitoneally administered, PD 149163. Injecting cisplatin diminished the serotonin level in the spinal cord, but intrathecal or intraperitoneal administration of PD 149163 did not affect this reduction. Conclusions: NTSR1 played a critical role in modulating CIPN-related pain. Therefore, NTSR1 agonists may be useful therapeutic agents to treat CIPN. In addition, spinal serotonin receptors may be indirectly involved in the effect of NTSR1 agonist.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.3
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• pp.227-234
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• 2000

Many reports suggest that neurotensin (NT) in the gastrointestinal tract may play a possible role as a neurotransmitter, a circulating hormone, or a modulator of motor activity. NT exerts various actions in the intestine; it produces contractile and relaxant responses in intestinal smooth muscle. This study was designed to investigate the effect of NT on motility of antral circular muscle strips in guinea-pig stomach. To assess the role of $Ca^{2+}$ influx in underlying mechanism, slow waves were simultaneously recorded with spontaneous contractions using conventional intracellular microelectrode technique. At the concentration of $10^{-7}$ M, where NT showed maximum response, NT enhanced the magnitude $(863{\pm}198%,\;mean\;SEM,\;n=13)$ and the frequency $(154{\pm}10.3%,\;n=11)$ of spontaneous contractions. NT evoked a slight hyperpolarization of membrane potential, tall and steep slow waves with abortive spikes $(278{\pm}50%,\;n=4).$ These effects were not affected by atropine $(2\;{\mu}M),$ guanethidine $(2\;{\mu}M)$ and tetrodotoxin (0.2μM). NT-induced contractile responses were abolished in $Ca^{2+}-free$ solution and reduced greatly to near abolition by $10\;{\mu}M$ of verapamil or 0.2 mM of $CdCl_2.$ Verapamil attenuated the effects of NT on frequency and amplitude of the slow waves. Taken together, these results indicate that NT enhances contractility in guinea-pig gastric antral circular muscle and $Ca^{2+}$ influx through the voltage-operated $Ca^{2+}$ channel appears to play an important role in the NT-induced contractile mechanism.

• Experimental and Molecular Medicine
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• v.50 no.11
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• pp.4.1-4.13
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• 2018

Two-pore domain $K^+$ (K2P) channels have been shown to modulate neuronal excitability. The physiological role of TWIK-1, the first identified K2P channel, in neuronal cells is largely unknown, and we reported previously that TWIK-1 contributes to the intrinsic excitability of dentate gyrus granule cells (DGGCs) in mice. In the present study, we investigated the coexpression of TWIK-1 and TASK-3, another K2P member, in DGGCs. Immunohistochemical staining data showed that TASK-3 proteins were highly localized in the proximal dendrites and soma of DGGCs, and this localization is similar to the expression pattern of TWIK-1. TWIK-1 was shown to associate with TASK-3 in DGGCs of mouse hippocampus and when both genes were overexpressed in COS-7 cells. shRNA-mediated gene silencing demonstrated that TWIK-1/TASK-3 heterodimeric channels displayed outwardly rectifying currents and contributed to the intrinsic excitability of DGGCs. Neurotensin-neurotensin receptor 1 (NT-NTSR1) signaling triggered the depolarization of DGGCs by inhibiting TWIK-1/TASK-3 heterodimeric channels, causing facilitated excitation of DGGCs. Taken together, our study clearly showed that TWIK-1/TASK-3 heterodimeric channels contribute to the intrinsic excitability of DGGCs and that their activities are regulated by NT-NTSR1 signaling.