beta-Lactotensin derived from bovine beta-lactoglobulin suppresses food intake via the CRF system followed by the CGRP system in mice.
We found that beta-lactotensin (His-Ile-Arg-Leu), which has been isolated as an ileum-contracting peptide from chymotrypsin digest of bovine beta-lactoglobulin, dose-dependently suppresses food intake after intracerebroventricular (i.c.v.) or intraperitoneal administration at a dose of 40 nmol/mouse or 100mg/kg, respectively, in fasted mice. Orally administered beta-lactotensin also suppressed food intake at 500 mg/kg. We previously reported that beta-lactotensin acts as an agonist for neurotensin receptors; however, the anorexigenic activity of beta-lactotensin was not inhibited by i.c.v. co-administration with SR48692 or levocabastine, an antagonist for neurotensin NT(1) or NT(2) receptor, respectively. On the other hand, the anorexigenic effect of beta-lactotensin was blocked by i.c.v. co-administration with astressin or calcitonin gene-related peptide (CGRP)(8-37), an antagonist for corticotropin releasing factor (CRF) or CGRP, respectively. beta-Lactotensin had affinity for neither CRF nor CGRP receptor. In addition, CRF-induced anorexigenic activity after i.c.v. administration was completely blocked by CGRP(8-37), while CGRP-induced anorexigenic activity was not inhibited by astressin. These results suggest that the CGRP system is activated downstream of the CRF system in food intake regulation. Taken together, beta-lactotensin may suppress food intake by activating the CRF system followed by the CGRP system, independently of the neurotensin system.
Hou
I-Ching
IC
Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho Uji, Kyoto 611-0011, Japan.
Yoshikawa
Masaaki
M
Ohinata
Kousaku
K
D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D004435:Eating / Q000187:drug effects*; D007782:Lactoglobulins / Q000378:metabolism*; D008297:Male; D051379:Mice; D009842:Oligopeptides / Q000378:metabolism* / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D018028:Receptors, Neurotensin / Q000037:antagonists & inhibitors / Q000378:metabolism
D007782:Lactoglobulins; D009842:Oligopeptides; D010446:Peptide Fragments; D010880:Piperidines; D018028:Receptors, Neurotensin; C102984:beta-lactotensin; C104416:astressin; D003346:Corticotropin-Releasing Hormone; C047340:levocabastine