Enzymatic degradation of luteinizing hormone releasing hormone (LHRH) by mucosal homogenates from the intestine of the common brushtail possum (Trichosurus vulpecula).
The peptidolytic activity of fresh and frozen mucosal homogenates from five regions (duodenum, jejunum, ileum, caecum and colon) of possum intestine from Trichosurus vulpecula towards human Luteinizing Hormone Releasing Hormone (LHRH) was investigated. The rank of order of specific peptidolytic activity of the mucosal homogenates was jejunum > ileum > caecum> duodenum = colon, with a 3 to 4 fold difference between the least and the most active segment in both frozen and fresh samples. The formation of peptides LHRH (1-3), LHRH (1-4) and LHRH (1-5) suggest endopepetidase-24.18, endopeptidase-24.15 and angiotensin converting enzyme (ACE) might be responsible for the peptide degradation in mucosal homogenates. The inhibition of LHRH degradation by mucosal homogenates was evaluated in four regions (jejunum, ileum, caecum and colon) of possum intestine. Ethylenediaminetetraacetic acid (EDTA, 5 mM), sodium deoxycholate (SDA, 10 mM) and bacitracin (3.5 or 9 mM) inhibited the degradation of LHRH in mucosal homogenates from small intestine and hindgut. However, the serine protease inhibitor, soybean trypsin-chymotrypsin inhibitor (SBTI), did not prevent degradation of LHRH. It is concluded that combining peptides with inhibitors may enhance oral delivery of bioactive peptides or proteins to possums.
Wen
J Y
JY
School of Pharmacy, University of Otago, PO Box 913, Dunedin, New Zealand.
Ledger
R
R
McLeod
B J
BJ
Davies
N M
NM
Butt
A G
AG
Tucker
I G
IG
D000818:Animals; D010450:Endopeptidases / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008871:Microvilli / Q000201:enzymology; D009893:Opossums / Q000502:physiology*; D011480:Protease Inhibitors / Q000494:pharmacology; D014020:Tissue Extracts / Q000378:metabolism*
D011480:Protease Inhibitors; D014020:Tissue Extracts; D007987:Gonadotropin-Releasing Hormone; D010450:Endopeptidases