• Archives of Pharmacal Research
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• v.18 no.2
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• pp.121-128
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• 1995

The role of nitric oxide (NO) in non-adrenegic non-cholinergic (NANC) neurotransmission was studied on circular muscle strips of the dorsal part of the fuinea-pig gastric fundus. In the presence of atropine and guanethidine, a low frequency-dependent relaxsations which were not affected by adrenergic and cholinergic blockage but abolished by tetrodotoxin. $N^G$-nitro-L-arginine (L-NNA), a stereospecific inhibitor of NO-biosynthesis, inhibited the relaxations induced by electrical stiumulations but not the relaxations to exogenous nitric oxide. The effect of L-NNA was prevented by L-arginine, the precursor of the NO biosynthesis but not by its enantiomer, D-arginine. Exgenous administration of No caused concentration -dependent relaxations which showed a similarity to those obtained with electrical simultaion. Hemoglobin, a NOscavenger, abolished the NO-induced relaxations and also markedly reduced those induced by electrical simultaion. The inhibitory effect os hemoglobin was similar to that of L-NNA. Application of ATP caused weak relaxations compared with those to electrical stimultaion, which were unaffected by L-NNA. Exogenously applied vasoactive intestinal polypeptide (VIP) induced concentration-dependent relaxation which was not affected by L-NNA. These results suggest that NO is produced and released mainly as a neurotransmitter from enteric neurons during NANC relaxation induced by low frequencies and short trains of electrical simulation and has a main role in NANC neurotransmission at relaxation induced by these electrical simultaions in the guinea-pig gastric fundus.

• 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.

• Archives of Obesity and Metabolism
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• v.1 no.1
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• pp.4-13
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• 2022

Currently, pharmacotherapy is becoming essential for obesity, owing to its expanding and increasing epidemiology. In this review, novel peptide-based drugs of four classes are covered: GLP-1 receptor agonist, GIP/GLP-1 receptor dual agonist, glucagon/GLP-1 receptor dual agonist, and a combination of amylin receptor agonist/GLP-1 receptor agonist. Semaglutide is a next-generation GLP-1 receptor agonist with a longer duration and stronger weight and glucose reduction effects than liraglutide and dulaglutide. In the STEP1 trial, semaglutide 2.4 mg reduced body weight by approximately 15% in people with obesity with similar or milder adverse events than liraglutide 3.0 mg. Tirzepatide, a GIP/GLP-1 receptor dual agonist, also has a long duration and strong weight- and glucose-lowering effect. According to SURPASS-2, 3, and 4, in patients with BMI≥25 kg/m² and type 2 diabetes mellitus (T2DM), tirzepatide 15 mg reduced the initial body weight by >13%. Cotadutide, a glucagon/GLP-1 receptor dual agonist, showed weaker weight-lowering effects than semaglutide and tirzepatide, while it was comparable to that of liraglutide in a phase 2 clinical trial for non-alcoholic fatty liver disease in patients with BMI≥25 kg/m² and T2DM. Additionally, its effect on the liver was noticeable. The long-acting amylin receptor agonist cargrilintide combined with semaglutide can be another effective option for obesity treatment. Even in a small phase 1 trial with a short study period of 20 weeks, cargrilintide 2.4 mg/semaglutide 2.4 mg reduced by 17% of initial body weight in people with BMI 27-39.9 kg/m². In coming several years, semaglutide, tirzepatide, and cargrilintide/semaglutide will become available for obesity treatment in Korea.