A recombinant rat vascular AT1 receptor confers growth properties to angiotensin II in Chinese hamster ovary cells.
A rat vascular AT1 receptor cDNA has been stably expressed into Chinese Hamster Ovary cells and the resulting recombinant AT1a receptor has been functionally characterized. This receptor binds 125I Sar1-angiotensin II with an affinity of 0.9 nM and the displacement of this ligand by a series of peptidic and nonpeptidic analogs is shown. Binding of angiotensin II to this receptor causes a rapid increase in inositol phosphate production, whereas this effect is not observed in nontransfected cells. Des-aspartyl1 angiotensin II and at a lesser extent angiotensin I are also able to produce an increase in inositol phosphates. More importantly, the actions of angiotensin II on cell division were clearly demonstrated in this model, since angiotensin II is able to stimulate DNA synthesis by 400% and double the cell population of the transfected cells in 36 hours in the absence of any other growth factor, whereas no effect is observed in nontransfected cells.
Teutsch
B
B
Institut National de la Santé et de la Recherche Médicale Unité 36, Collège de France, Paris.
Bihoreaú
C
C
Monnot
C
C
Bernstein
K E
KE
Murphy
T J
TJ
Alexander
R W
RW
Corvol
P
P
Clauser
E
E
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D016466:CHO Cells; D002455:Cell Division; D006224:Cricetinae; D004247:DNA / Q000096:biosynthesis; D007295:Inositol Phosphates / Q000502:physiology; D007328:Insulin / Q000494:pharmacology; D051381:Rats; D011945:Receptors, Angiotensin / Q000502:physiology*; D011994:Recombinant Proteins / Q000502:physiology; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000502:physiology
D007295:Inositol Phosphates; D007328:Insulin; D011945:Receptors, Angiotensin; D011994:Recombinant Proteins; D000804:Angiotensin II; D004247:DNA; D010738:Type C Phospholipases