Angiotensin II-mediated cellular responses: a role for the 3′-untranslated region of the angiotensin AT1 receptor

We have previously demonstrated that Chinese hamster ovary (CHO) cells transfected with the angiotensin II AT 1 receptor gene containing only the coding region, presented tachyphylaxis to the total inositol phosphate (InsP s ) and Ca 2+ responses mediated by angiotensin II and [2-lysine]angiotensin II ([Lys 2 ]angiotensin II). Now we have evaluated the possible role of the 3′-untranslated region of the angiotensin AT 1 receptor mRNA in modulating the angiotensin AT 1 receptor-mediated cellular responses. The binding parameters, as well as the Ca 2+ and InsP s responses induced by angiotensin II and [Lys 2 ]angiotensin II were similar in cells transfected with the angiotensin AT 1 receptor with or without the 3′-untranslated region sequence. In cells transfected with the receptor containing the 3′-untranslated region sequence, angiotensin II-induced Ca 2+ and InsP s responses were desensitized by repeated stimulations, whereas [Lys 2 ]angiotensin II caused desensitization of InsP s production but not of Ca 2+ uptake in these cells. Our results suggest that the 3′-untranslated region plays a role in modulating cell signalling involved in the tachyphylaxis of angiotensin AT 1 receptor-mediated Ca 2+ responses.