Intracellular angiotensin II inhibits heterologous receptor stimulated Ca2+ entry

Recent studies show that angiotensin II (AngII) can act from within the cell, possibly via intracellular receptors pharmacologically different from typical plasma membrane AngII receptors. The role of this intracellular AngII (AngII(i)) is unclear. Besides direct effects of AngII(i) on cellular processes one could hypothesise a possible role of AngII(i) in modulation of cellular responses induced after heterologous receptor stimulation. We therefore examined if AngIIi influences [Ca2+](i) in A7r5 smooth muscle cells after 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 administration of the AT(1)-antagonist losartan and not influenced by the AT(2)-antagonist PD123319. Similar results were obtained in single cell [Ca2+](i) measurements, showing that AngII(i) predominantly influences Ca2+ influx and not Ca2+ release via AT(1)-like receptors. It is concluded that AngII(i) modulates signal transduction activated by heterologous receptor stimulation. (C) 2001 Elsevier Science Inc. All rights reserved.