An amino-terminal fragment of LCRF, LCRF-(1-35), has the same activity as the natural peptide.
A cholecystokinin (CCK)-releasing peptide, luminal CCK-releasing factor (LCRF), has been purified from rat jejunal secretion. Amino acid analysis and mass spectral analysis showed that the purified peptide is composed of 70-75 amino acid residues and has a mass of 8,136 Da. Microsequence analysis of LCRF yielded an amino acid sequence for the amino-terminal 41 residues. To determine the biologically active region of the molecule, a peptide was synthesized consisting of the amino-terminal 35 amino acids of LCRF. In this study, intraduodenal infusion of LCRF-(1-35) significantly stimulated pancreatic secretion in conscious rats. The dose-response curves to LCRF-(1-35) and to monitor peptide were similar and biphasic, with higher doses producing submaximal pancreatic secretory responses. The CCK-A receptor antagonist MK-329 abolished the pancreatic secretory response to intraduodenally infused LCRF-(1-35). These results demonstrate that LCRF biological activity is contained within the amino-terminal 35-amino acid portion of LCRF, and this fragment may be useful for investigating the role of LCRF in gastrointestinal function.
Spannagel
A W
AW
Department of Physiology, University of Texas Health Science Center, San Antonio 78284-7756, USA.
Reeve
J R
JR
Liddle
R A
RA
Guan
D
D
Green
G M
GM
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D020109:Devazepide; D004386:Duodenum; D005768:Gastrointestinal Hormones / Q000494:pharmacology*; D006133:Growth Substances / Q000494:pharmacology*; D006727:Hormone Antagonists / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008970:Molecular Weight; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D010189:Pancreatic Juice / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012844:Sincalide / Q000037:antagonists & inhibitors; D014359:Trypsin Inhibitor, Kazal Pancreatic
D001570:Benzodiazepinones; D005768:Gastrointestinal Hormones; D006133:Growth Substances; D006727:Hormone Antagonists; D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments; C504705:Spink1 protein, rat; D014359:Trypsin Inhibitor, Kazal Pancreatic; D020109:Devazepide; D012844:Sincalide