Evidence for changes in the tachyphylactic property of recombinant angiotensin II AT(1) receptor expressed in CHO cells.
The manifestation of tachyphylaxis to angiotensin II in Chinese hamster ovary (CHO) cells expressing the rat angiotensin II AT(1) receptor was investigated. The cells were transfected with a cDNA fragment containing the complete coding region of the angiotensin II AT(1A) receptor gene, as well as 56 bp of its 3'- and 52 bp of its 5'-untranslated regions. These cells (CHO-AT(1)) responded to angiotensin II by increases in intracellular Ca(2+) concentration and inositol phosphate turnover, which were inhibited upon repeated administrations, characterizing the tachyphylaxis phenomenon. In contrast to smooth muscle cells, which are rendered tachyphylactic to angiotensin II but not to [2-lysine]angiotensin II ([Lys(2)]angiotensin II), this analogue induced responses in CHO-AT(1) cells that were also inhibited upon repeated administrations. A smooth muscle cell line, which showed tachyphylaxis only to angiotensin II, became tachyphylactic also to [Lys(2)]angiotensin II after transfection with the angiotensin II AT(1) receptor gene. Our findings suggest that posttranscriptional control directed by the 3'- or the 5'-untranslated regions in the angiotensin II AT(1) receptor gene may play a role in modulating the signal transduction pathways involved in the mechanism of angiotensin II tachyphylaxis.
França
Lucimar P
LP
Department of Biophysics, Universidade Federal de São Paulo-Escola Paulista de Medicina, Rua Botucatu 862, 04023-060, São Paulo, SP, Brazil.
Corrêa
Silvana A A
SA
Barbosa
Ana M R B
AM
Ferreira
Alice T
AT
Han
Sang W
SW
Shimuta
Suma I
SI
Paiva
Antonio C M
AC
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D006224:Cricetinae; D004274:DNA, Recombinant / Q000235:genetics; D015870:Gene Expression; D005998:Glycine / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism; D007552:Isotonic Solutions / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D013618:Tachyphylaxis / Q000502:physiology*; D014162:Transfection
D004274:DNA, Recombinant; D007295:Inositol Phosphates; D007552:Isotonic Solutions; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; C037692:Tyrode's solution; D000804:Angiotensin II; C058393:angiotensin II, Lys(2)-; D000255:Adenosine Triphosphate; D002118:Calcium; D005998:Glycine