Nonsulfated cholecystokinins in the small intestine of pigs and rats |
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| Affiliation: | 1. Mass Spectrometry Centre, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal;2. QOPNA, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal;3. Institute for Biomedicine—iBiMED, Health Sciences Program, University of Aveiro, Portugal;1. Vagal Afferent Research Group, Centre for Nutrition and Gastrointestinal Diseases, Discipline of Medicine, University of Adelaide, Adelaide, South Australia, Australia;2. South Australian Health and Medical Research Institute (SAHMRI), Adelaide, South Australia, Australia;3. Royal Adelaide Hospital, Adelaide, South Australia, Australia;1. Department of Pharmacology, Medical School of Ribeirão Preto, Universidade de São Paulo, 14049-900 Ribeirão Preto, SP, Brazil;2. Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil;3. Department of Phamacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil;4. Department of Pathology, Medical School of Ribeirão Preto Campus, Universidade de São Paulo, Ribeirão Preto, SP, Brazil;1. Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia;2. SAAD Centre for Pharmacy and Diabetes, School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, UK |
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| Abstract: | Cholecystokinin (CCK) is a gut hormone that acts via two receptors. The CCKA-receptor requires the tyrosyl residue in the C-terminal bioactive site of CCK to be O-sulfated, whereas, the CCKB-receptor binds irrespective of sulfation. Consequently, unsulfated CCK peptides – if present – may constitute a hormone system that acts only through the CCKB-receptor. Therefore, we have now examined whether, CCK peptides occur in nonsulfated form in the small intestine of pigs and rats. The concentrations of sulfated and nonsulfated CCK were measured by RIAs, one specific for sulfated CCKs and a new two-step assay specific for nonsulfated CCK. For further characterization, the intestinal extracts were subjected to size- and ion exchange-chromatography.The intestinal concentrations of sulfated and nonsulfated CCK were highest in the duodenum and the proximal part of jejunum both in the pig and the rat. The porcine duodenal mucosa contained 193 ± 84 pmol/g sulfated CCK and 31 ± 10 pmol/g nonsulfated CCK, and the upper rat intestine 70 ± 19 pmol/g and 8 ± 2 pmol/g, respectively. The degree of sulfation correlated with the endoproteolytic proCCK processing. Thus, 38% of porcine CCK-58 was unsulfated, whereas, only 12% of CCK-8 was unsulfated.The results show that a substantial part of intestinal CCK peptides in rats and pigs are not sulfated, and that the longer peptides (CCK-58 and CCK-33) are less sulfated than the shorter (CCK-22 and CCK-8). Hence, the results demonstrate that proCCK in the gut is processed both to sulfated and unsulfated α-amidated peptides of which the latter are assumed to act via the CCKB-receptor. |
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| Keywords: | Nonsulfated cholecystokinin Cholecystokinin Gastrin Gut hormones Posttranslational modification Tyrosyl O-sulfation |
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