Rhamnose moiety of phosphoramidon is not required for in vivo inhibition of endothelin converting enzyme.
Experiments were conducted to determine the importance of the carbohydrate moiety of phosphoramidon in the inhibition of the pressor response to big endothelin-1 in anesthetized rats. Big endothelin-1 produced a 42% increase in mean arterial pressure which was nearly abolished by co-infusion of phosphoramidon. Similarly, when an analog of phosphoramidon lacking the rhamnose group (phosphoryl-leu-trp-OH) was co-infused, a significant attenuation of the pressor response was observed. These findings indicate that the rhamnose moiety of phosphoramidon is not responsible for the distinguishing this compound as an inhibitor of the response to big endothelin-1 in the rat.
Pollock
D M
DM
Abbott Laboratories, Abbott Park, IL 60064.
Shiosaki
K
K
Sullivan
G M
GM
Opgenorth
T J
TJ
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D001794:Blood Pressure / Q000187:drug effects*; D004151:Dipeptides / Q000494:pharmacology*; D019332:Endothelin-1; D000072396:Endothelin-Converting Enzymes; D016232:Endothelins / Q000494:pharmacology*; D006020:Glycopeptides / Q000494:pharmacology*; D008297:Male; D008666:Metalloendopeptidases; D011498:Protein Precursors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012210:Rhamnose; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D004151:Dipeptides; D019332:Endothelin-1; D016232:Endothelins; D006020:Glycopeptides; D011498:Protein Precursors; C048510:N-phosphorylleucyltryptophan; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes; D012210:Rhamnose; C008890:phosphoramidon