Formation of angiotensin-(1-7) from angiotensin II by the venom of Conus geographus.
The binding of [3H]angiotensin II to AT(1) receptors on Chinese Hamster Ovary cells expressing the human AT(1) receptor (CHO-AT(1) cells) is potently inhibited by venoms of the marine snails Conus geographus and C. betulinus. On the other hand, the binding of the nonpeptide AT(1) receptor-selective antagonist [3H]candesartan is not affected but competition binding curves of angiotensin II and the peptide antagonist [Sar(1),Ile(8)]angiotensin II (sarile) are shifted to the right. These effects resulted from the breakdown of angiotensin II into smaller fragments that do not bind to the AT(1) receptor. In this context, angiotensin-(1-7) is the most prominent fragment and angiotensin-(1-4) and angiotensin-(1-5) are also formed but to a lesser extent. The molecular weight of the involved peptidases exceeds 50 kDa, as determined by gel chromatography and ultrafitration.
Le
Minh Tam
MT
Department of Molecular and Biochemical Pharmacology, Institute for Molecular Biology and Biotechnology, Free University of Brussels (VUB), Paardenstraat 65, B-1640 Sint-Genesius Rode, Belgium. tmleminh@vub.ac.be
Vanderheyden
Patrick M L
PM
Baggerman
Geert
G
Broeck
Jozef Vanden
JV
Vauquelin
Georges
G
D000803:Angiotensin I; D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D010446:Peptide Fragments / Q000378:metabolism*; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000235:genetics / Q000378:metabolism*; D014316:Tritium; D020866:omega-Conotoxin GVIA / Q000378:metabolism*
D010446:Peptide Fragments; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D014316:Tritium; D000804:Angiotensin II; D000803:Angiotensin I; D020866:omega-Conotoxin GVIA; C118790:angiotensin I (1-7)