The Combination of Cholecystokinin and Stress Amplifies an Inhibition of Appetite, Gastric Emptying, and an Increase in c-Fos Expression in Neurons of the Hypothalamus and the Medulla Oblongata.
Cholecystokinin (CCK) had been the first gastrointestinal hormone known to exert anorexic effects. CCK had been inferred to contribute to the onset of functional dyspepsia (FD) symptoms. To understand the pathophysiology of FD, the roles of stress have to be clarified. In this study, we aimed to clarify the influence of stress on the action of cholecystokinin (CCK) on appetite and gastric emptying. Using rats, stress was simulated by giving restraint stress or intraperitoneal injection of the stress-related peptide hormone urocortin 1 (UCN1). The effects of CCK and restraint stress, alone or in combination, on food intake and gastric motility were examined, and c-Fos expression in the neurons of appetite control network in the central nervous system was assessed by immunohistochemical staining. CCK inhibited food intake and gastric emptying in a dose-dependent manner. Food intake for 1 h was significantly lower with UCN1 (2 nmol/kg) than with the saline control. Restraint stress amplified the suppressive effects of CCK on food intake for 1 h and on gastric emptying. With regard to brain function, the CCK induced c-Fos expression in the neurons of the nucleus tractus solitarius and paraventricular nucleus of the hypothalamus was markedly and significantly amplified by the addition of restraint stress with CCK. The results suggested that stress might amplify the anorexic effects of CCK through activation of the nuclei that comprise the brain neuronal network for satiation; this might play a role in the pathogenesis of the postprandial distress syndromes of functional dyspepsia.
['Yamaguchi|Naomi|N|', 'Hosomi|Eriko|E|', 'Hori|Yutaro|Y|', 'Ro|Shoki|S|', 'Maezawa|Kosuke|K|', 'Ochiai|Mitsuko|M|', 'Nagoshi|Sumiko|S|', 'Takayama|Kiyoshige|K|', 'Yakabi|Koji|K|http://orcid.org/0000-0002-9917-5542']
D000818:Animals D001066:Appetite D001921:Brain D002766:Cholecystokinin D004415:Dyspepsia D004435:Eating D005746:Gastric Emptying D008297:Male D009474:Neurons D016760:Proto-Oncogene Proteins c-fos D017207:Rats, Sprague-Dawley D013315:Stress, Psychological D054832:Urocortins
Cholecystokinin Stress Gastric emptying c-Fos Urocortin 1