INTERNALIZATION OF THE RAT AT(1A) AND AT(1B) RECEPTORS - PHARMACOLOGICAL AND FUNCTIONAL REQUIREMENTS

The capacity of the angiotensin II (AngII) agonist [Sar1]AngII, the an tagonist [Sar1-Ile8]AngII and the non-peptidic antagonist DuP753 to un dergo receptor internalization were studied in Chinese hamster ovary c ells expressing rat AngII type 1a or 1b receptors (AT(1a) or AT(1b)) o r a mutant of AT(1a) (Asn(74)) unable to couple G-protein. In this exp ression system, the ligand-induced internalization of rat AT(1a) and A T(1b) are similar. Moreover, peptidic ligands, either the agonist or a ntagonist, induce a significant internalization of AT(1) receptors, bu t the non-peptidic antagonist DuP753 is far less potent. Finally, the normal internalization of the mutant Asn(74) demonstrates that recepto r activation and G-protein coupling are not required for AT(1a) intern alization.