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 (AngIIi) is unclear. Besides direct effects of AngIIi on cellular processes one could hypothesise a possible role of AngIIi in modulation of cellular responses induced after heterologous receptor stimulation. We therefore examined if AngIIi influences [Ca+]i in A7r5 smooth muscle cells after serotonin (5HT) or UTP receptor stimulation. Application of AngIIi using liposomes, markedly inhibited 45Ca2+ influx after receptor stimulation with 5HT or UTP. This inhibition was reversible by intracellular administration of the AT1-antagonist losartan and not influenced by the AT2-antagonist PD123319. Similar results were obtained in single cell [Ca2+]i measurements, showing that AngIIi predominantly influences Ca2+ influx and not Ca2+ release via AT1-like receptors. It is concluded that AngIIi modulates signal transduction activated by heterologous receptor stimulation.
Filipeanu
C M
CM
Groningen University Institute for Drug Exploration (GUIDE), Department of Clinical Pharmacology, University of Groningen, The Netherlands.
Brailoiu
E
E
Henning
R H
RH
Deelman
L E
LE
de Zeeuw
D
D
Nelemans
S A
SA
D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D008081:Liposomes; D019808:Losartan / Q000494:pharmacology; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology; D014544:Uridine Triphosphate / Q000494:pharmacology
D007093:Imidazoles; D008081:Liposomes; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D000804:Angiotensin II; C073402:PD 123319; D012701:Serotonin; D019808:Losartan; D002118:Calcium; D014544:Uridine Triphosphate