Prolactin-releasing peptide (PrRP) has been proposed to mediate the central satiating effects of cholecystokinin (CCK) through the vagal CCK1 receptor. PrRP acts as an endogenous ligand of G protein-coupled receptor 10 (GPR10), which is expressed at the highest levels in brain areas related to food intake regulation, e.g., the paraventricular hypothalamic nucleus (PVN) and nucleus of the solitary tract (NTS). The NTS and PVN are also significantly activated after peripheral CCK administration. The aim of this study was to determine whether the endogenous PrRP neuronal system in the brain is involved in the central anorexigenic effect of the peripherally administered CCK agonist JMV236 or the CCK1 antagonist devazepide and whether the CCK system is involved in the central anorexigenic effect of the peripherally applied lipidized PrRP analog palm-PrRP31 in fasted lean mice. The effect of devazepide and JMV236 on the anorexigenic effects of palm-PrRP31 as well as devazepide combined with JMV236 and palm-PrRP31 on food intake and Fos cell activation in the PVN and caudal NTS was examined. Our results suggest that the anorexigenic effect of JMV236 is accompanied by activation of PrRP neurons of the NTS in a CCK1 receptor-dependent manner. Moreover, while the anorexigenic effect of palm-PrRP31 was not affected by JMV236, it was partially attenuated by devazepide in fasted mice. The present findings indicate that the exogenously influenced CCK system may be involved in the central anorexigenic effect of peripherally applied palm-PrRP31, which possibly indicates some interaction between the CCK and PrRP neuronal systems.

• MeSH
• anorektika aplikace a dávkování   MeSH
• antagonisté hormonů aplikace a dávkování   MeSH
• chemokiny CC účinky léků   metabolismus   MeSH
• cholecystokinin metabolismus   MeSH
• devazepid aplikace a dávkování   MeSH
• hormon uvolňující prolaktin aplikace a dávkování   analogy a deriváty   MeSH
• injekce intraperitoneální MeSH
• injekce subkutánní MeSH
• myši inbrední C57BL MeSH
• nucleus paraventricularis hypothalami účinky léků   metabolismus   MeSH
• nucleus solitarius účinky léků   metabolismus   MeSH
• omezení příjmu potravy MeSH
• peptidové fragmenty aplikace a dávkování   MeSH
• přijímání potravy účinky léků   MeSH
• protoonkogenní proteiny c-fos metabolismus   MeSH
• signální transdukce MeSH
• sinkalid aplikace a dávkování   analogy a deriváty   MeSH
• stravovací zvyklosti účinky léků   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: CART (cocaine- and amphetamine-regulated transcript) peptide and cholecystokinin (CCK) are neuromodulators involved in feeding behavior. This study is based on previously found synergistic effect of leptin and CCK on food intake and our hypothesis on a co-operation of the CART peptide and CCK in food intake regulation and Fos activation in their common targets, the nucleus tractus solitarii of the brainstem (NTS), the paraventricular nucleus (PVN), and the dorsomedial nucleus (DMH) of the hypothalamus. RESULTS: In fasted C57BL/6 mice, the anorexigenic effect of CART(61-102) in the doses of 0.1 or 0.5 microg/mouse was significantly enhanced by low doses of CCK-8 of 0.4 or 4 microg/kg, while 1 mg/kg dose of CCK-A receptor antagonist devazepide blocked the effect of CART(61-102) on food intake. After simultaneous administration of 0.1 microg/mouse CART(61-102) and of 4 microg/kg of CCK-8, the number of Fos-positive neurons in NTS, PVN, and DMH was significantly higher than after administration of each particular peptide. Besides, CART(61-102) and CCK-8 showed an additive effect on inhibition of the locomotor activity of mice in an open field test. CONCLUSION: The synergistic and long-lasting effect of the CART peptide and CCK on food intake and their additive effect on Fos immunoreactivity in their common targets suggest a co-operative action of CART peptide and CCK which could be related to synergistic effect of leptin on CCK satiety

• MeSH
• antagonisté hormonů farmakologie   MeSH
• benzodiazepinony farmakologie   MeSH
• devazepid farmakologie   MeSH
• fenylmočovinové sloučeniny farmakologie   MeSH
• financování organizované MeSH
• hubenost MeSH
• injekce intraperitoneální MeSH
• injekce intraventrikulární MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• neurony metabolismus   účinky léků   MeSH
• nucleus dorsomedialis hypothalami fyziologie   účinky léků   MeSH
• nucleus paraventricularis hypothalami fyziologie   účinky léků   MeSH
• nucleus solitarius fyziologie   účinky léků   MeSH
• pátrací chování fyziologie   účinky léků   MeSH
• peptidové fragmenty farmakologie   MeSH
• proteiny nervové tkáně farmakologie   MeSH
• protoonkogenní proteiny c-fos metabolismus   MeSH
• receptor cholecystokininu A antagonisté a inhibitory   MeSH
• receptor cholecystokininu B antagonisté a inhibitory   MeSH
• regulace chuti k jídlu fyziologie   účinky léků   MeSH
• sinkalid farmakologie   MeSH
• synergismus léků MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH