Angiotensin II desensitization and Ca2+ and Na+ fluxes in vascular smooth muscle cells.
The role of ion fluxes in angiotensin II (AII) desensitization (tachyphylaxis) was investigated by studying Na+ and Ca2+ translocation in cultured vascular smooth muscle cells from the rat aorta. The effects of AII were compared to those of [1-sarcosine]-AII (Sar1-AII), an analogue which also induces tachyphylaxis, and [2-lysine]-AII (Lys2-AII), an analogue that does not show this property. Maximally effective concentrations of the three peptides induced a rapid and transient increase in 45Ca2+ efflux, a rapid and sustained decrease in total cell Ca2+ and an increased Na+ permeability. Repeated treatments, at short intervals, with either of the three peptides abolished the effect on Ca2+ efflux, and this desensitization was slowly reversible. A 30-min rest period was sufficient for full recovery of the response of cells that were desensitized by Lys2-AII, whereas the recovery from AII or Sar1-AII-desensitization was still not complete after 60 min. Our results suggest that the difference in the behaviour of the "tachyphylactic" AII and Sar1-AII and the "non-tachyphylactic" Lys2-AII lays not in the production of different signals upon binding to the receptor, but in a difference in the hormone-receptor interaction itself.
Aboulafia
J
J
Escola Paulista de Medicina, Department of Biophysics, São Paulo, Brazil.
Oshiro
M E
ME
Feres
T
T
Shimuta
S I
SI
Paiva
A C
AC
D000804:Angiotensin II / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D001011:Aorta; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D002478:Cells, Cultured; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism*
D002132:Calcium Radioisotopes; D000804:Angiotensin II; C032651:angiotensin II, Sar(1)-Ile(5)-; C058393:angiotensin II, Lys(2)-; D012964:Sodium; D002118:Calcium