caa a22 4500 445888768 CHVBK 20180317145608.0 cr unu---uuuuu 170323e20110401xx s 000 0 eng 10.1007/s00535-010-0366-6 doi (NATIONALLICENCE)springer-10.1007/s00535-010-0366-6 Food intake and interdigestive gastrointestinal motility in ghrelin receptor mutant rats [Elektronische Daten] [Mehmet Bülbül, Reji Babygirija, Jun Zheng, Kirk Ludwig, Haiyan Xu, Jozef Lazar, Toku Takahashi] Background: Ghrelin is the endogenous ligand for the growth hormone secretagogue receptor (GHSR). Ghrelin regulates feeding activity and interdigestive contractions of the stomach in rodents. To investigate the role of endogenous ghrelin in the digestive system, we have developed GHSR-mutant rats, named FHH-Ghsrm1Mcwi, using the Fawn-Hooded Hypertensive (FHH) parental strain. Methods: N-ethyl-N-nitrosourea (ENU) was used as a mutagen. Genomic DNA prepared from a tail clip was analyzed using the targeting induced local lesions in genomes (TILLING) approach. The non-synonymous mutation in position 343 (NM_032075) led to the generation of a premature stop codon, causing deletion of the last 22 amino acids at the C-terminal of ghrelin receptor protein. Spontaneous and ghrelin-stimulated food intake was measured in wild-type (WT) FHH and FHH-Ghsrm1Mcwi rats. For interdigestive motility recording, two strain gauge transducers were sutured on the antrum and duodenum. Spontaneous gastroduodenal contractions were recorded in freely moving conscious rats. Results: Ghrelin (40μg/kg) failed to stimulate food intake in the mutant rats, while spontaneous food intake was not significantly different between the WT rats and FHH-Ghsrm1Mcwi rats. Phase III-like contractions were observed in stomach and duodenum both in the WT and FHH-Ghsrm1Mcwi rats. In the WT rats, ghrelin (12μg/kg) administration enhanced spontaneous phase III-like contractions, and a GHSR antagonist, (D-lys3)GHRP-6 (0.28mg/kg), abolished the spontaneous phase III-like contractions. In FHH-Ghsrm1Mcwi rats, ghrelin and (D-lys3)GHRP-6 did not affect phase III-like contractions. Conclusions: It is suggested that the intact GHSR structure is essential for the ghrelin-dependent regulation of interdigestive motility and feeding behavior. Even in FHH-Ghsrm1Mcwi rats, spontaneous gastric phase III-like contractions were still observed, suggesting the development of a compensatory mechanism to maintain these contractions. Springer, 2011 Ghrelin nationallicence GHSR-mutant nationallicence FHH rats nationallicence MMC nationallicence Food intake nationallicence Bülbül Mehmet Department of Surgery, Medical College of Wisconsin and Zablocki VA Medical Center, 5000 West National Avenue, 53295, Milwaukee, WI, USA aut Babygirija Reji Department of Surgery, Medical College of Wisconsin and Zablocki VA Medical Center, 5000 West National Avenue, 53295, Milwaukee, WI, USA aut Zheng Jun Department of Surgery, Medical College of Wisconsin and Zablocki VA Medical Center, 5000 West National Avenue, 53295, Milwaukee, WI, USA aut Ludwig Kirk Department of Surgery, Medical College of Wisconsin and Zablocki VA Medical Center, 5000 West National Avenue, 53295, Milwaukee, WI, USA aut Xu Haiyan Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, WI, USA aut Lazar Jozef Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, WI, USA aut Takahashi Toku Department of Surgery, Medical College of Wisconsin and Zablocki VA Medical Center, 5000 West National Avenue, 53295, Milwaukee, WI, USA aut Journal of Gastroenterology Springer Japan 46/4(2011-04-01), 469-478 0944-1174 46:4<469 2011 46 535 https://doi.org/10.1007/s00535-010-0366-6 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00535-010-0366-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Bülbül Mehmet Department of Surgery, Medical College of Wisconsin and Zablocki VA Medical Center, 5000 West National Avenue, 53295, Milwaukee, WI, USA aut NATIONALLICENCE 700 1- Babygirija Reji Department of Surgery, Medical College of Wisconsin and Zablocki VA Medical Center, 5000 West National Avenue, 53295, Milwaukee, WI, USA aut NATIONALLICENCE 700 1- Zheng Jun Department of Surgery, Medical College of Wisconsin and Zablocki VA Medical Center, 5000 West National Avenue, 53295, Milwaukee, WI, USA aut NATIONALLICENCE 700 1- Ludwig Kirk Department of Surgery, Medical College of Wisconsin and Zablocki VA Medical Center, 5000 West National Avenue, 53295, Milwaukee, WI, USA aut NATIONALLICENCE 700 1- Xu Haiyan Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, WI, USA aut NATIONALLICENCE 700 1- Lazar Jozef Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, WI, USA aut NATIONALLICENCE 700 1- Takahashi Toku Department of Surgery, Medical College of Wisconsin and Zablocki VA Medical Center, 5000 West National Avenue, 53295, Milwaukee, WI, USA aut NATIONALLICENCE 773 0- Journal of Gastroenterology Springer Japan 46/4(2011-04-01), 469-478 0944-1174 46:4<469 2011 46 535 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer