Use of protease inhibitors to improve calcitonin absorption from the smalland large intestine in rats

Citation
H. Tozaki et al., Use of protease inhibitors to improve calcitonin absorption from the smalland large intestine in rats, J PHARM PHA, 50(8), 1998, pp. 913-920
Citations number
26
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
JOURNAL OF PHARMACY AND PHARMACOLOGY
ISSN journal
0022-3573 → ACNP
Volume
50
Issue
8
Year of publication
1998
Pages
913 - 920
Database
ISI
SICI code
0022-3573(199808)50:8<913:UOPITI>2.0.ZU;2-2
Abstract
The objective of this study was to examine the effects of protease inhibito rs on the absorption of calcitonin from different regions of the intestine in rats. The absorption experiments were investigated by in-situ use of clo sed intestinal loops in rats and stability of calcitonin was examined in mu cosal homogenates and intestinal fluids. The intestinal absorption of calci tonin was evaluated by measurement of its hypocalcaemic effect. No substantial hypocalcaemic response was observed when calcitonin was admi nistered into the jejunum or colon. A slight hypocalcaemic effect was obser ved after administration of calcitonin into the ileum. Of the co-administer ed protease inhibitors, bacitracin (20 mM) strongly promoted calcitonin abs orption from the jejunum, ileum and colon. A significant hypocalcaemic effe ct was also obtained after intestinal administration of calcitonin with soy bean trypsin inhibitor (10 mg mL(-1)), camostat mesylate (20 mM) or aprotin in (2 mg mL(-1)). In the stability experiment, bacitracin reduced the degra dation of calcitonin in the different intestinal homogenates, Soybean tryps in inhibitor significantly reduced the degradation of calcitonin in the flu ids of the small intestine. We also examined the different endopeptidases i n gut luminal fluids and the different exopeptidases in gut mucosal homogen ates of rats. The ranking order for the total endopeptidase activity of the intestinal fluids was jejunum > ileum > colon. That for total exopeptidase activity of the intestinal mucosa was jejunum > ileum > colon, These results suggest that endo- and exopeptidases might be responsible for the hydrolysis of calcitonin and that protease inhibitors might usefully i mprove absorption of calcitonin to the systemic circulation from the large intestine.