Internalization of the rat AT1a and AT1b receptors: pharmacological and functional requirements.
The capacity of the angiotensin II (AngII) agonist [Sar1]AngII, the antagonist [Sar1-Ile8]AngII and the non-peptidic antagonist DuP753 to undergo receptor internalization were studied in Chinese hamster ovary cells expressing rat AngII type 1a or 1b receptors (AT1a or AT1b) or a mutant of AT1a (Asn74) unable to couple G-protein. In this expression system, the ligand-induced internalization of rat AT1a and AT1b are similar. Moreover, peptidic ligands, either the agonist or antagonist, induce a significant internalization of AT1 receptors, but the non-peptidic antagonist DuP753 is far less potent. Finally, the normal internalization of the mutant Asn74 demonstrates that receptor activation and G-protein coupling are not required for AT1a internalization.
Conchon
S
S
Institut National de la Santé et de la Recherche Médicale Unité 36 Collège de France, Paris.
Monnot
C
C
Teutsch
B
B
Corvol
P
P
Clauser
E
E
D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001692:Biological Transport; D001713:Biphenyl Compounds / Q000378:metabolism*; D016466:CHO Cells; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000378:metabolism*; D019808:Losartan; D051381:Rats; D011945:Receptors, Angiotensin / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013777:Tetrazoles / Q000378:metabolism*
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D011945:Receptors, Angiotensin; D011994:Recombinant Proteins; D013777:Tetrazoles; D000804:Angiotensin II; C009210:sarleucin; C074793:angiotensin II, Sar(1)-; D019808:Losartan