Intracellular angiotensin II inhibits heterologous receptor stimulated Ca2+ entry

Recent studies show that angiotensin II (AngII) can act from within the cel l, possibly via intracellular receptors pharmacologically different from ty pical plasma membrane AngII receptors. The role of this intracellular AngII (AngII(i)) is unclear. Besides direct effects of AngII(i) on cellular proc esses one could hypothesise a possible role of AngII(i) in modulation of ce llular responses induced after heterologous receptor stimulation. We theref ore examined if AngIIi influences [Ca2+](i) in A7r5 smooth muscle cells aft er serotonin (5HT) or UTP receptor stimulation. Application of AngIIi using liposomes, markedly inhibited Ca-45(2+) influx after receptor stimulation with 5HT or UTP. This inhibition was reversible by intracellular administra tion of the AT(1)-antagonist losartan and not influenced by the AT(2)-antag onist PD123319. Similar results were obtained in single cell [Ca2+](i) meas urements, showing that AngII(i) predominantly influences Ca2+ influx and no t Ca2+ release via AT(1)-like receptors. It is concluded that AngII(i) modu lates signal transduction activated by heterologous receptor stimulation. ( C) 2001 Elsevier Science Inc. All rights reserved.