Intracellular Angiotensin II Elicits CA²⁺ Increases in A7r5 Vascular Smooth Muscle Cells

Creator(s)

Catalin M. Filipeanu, University of Groningen, University Medical Center Groningen, Groningen University Institute for Drug Exploration (GUIDE)
Eugen Brailoiu, East Tennessee State University
Jan Willem Kok, University of Groningen, University Medical Center Groningen, Groningen University Institute for Drug Exploration (GUIDE)
Robert H. Henning, University of Groningen, University Medical Center Groningen, Groningen University Institute for Drug Exploration (GUIDE)
Dick De Zeeuw, University of Groningen, University Medical Center Groningen, Groningen University Institute for Drug Exploration (GUIDE)
S. Adriaan Nelemans, University of Groningen, University Medical Center Groningen, Groningen University Institute for Drug Exploration (GUIDE)

Document Type

Article

Publication Date

6-18-2001

Description

Recent studies show that angiotensin II can act within the cell, possibly via intracellular receptors pharmacologically different from typical plasma membrane angiotensin II receptors. The signal transduction of intracellular angiotensin II is unclear. Therefore, we investigated the effects of intracellular angiotensin II in cells devoid of physiological responses to extracellular angiotensin II (A7r5 vascular smooth muscle cells). Intracellular delivery of angiotensin II was obtained by using liposomes or cell permeabilisation. Intracellular angiotensin II stimulated Ca2+ influx, as measured by 45Ca2+ uptake and single-cell fluorimetry. This effect was insensitive to extracellular or intracellular addition of losartan (angiotensin AT1 receptor antagonist) or PD123319 ((s)-1-(4-[dimethylamino]-3-methylphenyl)methyl-5-(diphenylacetyl)-4,5,6,7- tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylate) (angiotensin AT2 receptor antagonist). Intracellular angiotensin II stimulated inositol-1,4,5-trisphosphate (Ins(1,4,5,)P3) production and increased the size of the Ins(1,4,5,)P3 releasable 45Ca2+ pool in permeabilised cells, independent of losartan and PD123319. Small G-proteins did not participate in this process, as assessed by using GDPβS. Intracellular delivery of angiotensin I was unable to elicit any of the effects elicited by intracellular angiotensin II. We conclude from our intracellular angiotensin application experiments that angiotensin II modulates Ca2+ homeostasis even in the absence of extracellular actions. Pharmacological properties suggest the involvement of putative angiotensin non-AT1-/non-AT2 receptors.

Citation Information

Filipeanu, Catalin M.; Brailoiu, Eugen; Kok, Jan Willem; Henning, Robert H.; De Zeeuw, Dick; and Nelemans, S. Adriaan. 2001. Intracellular Angiotensin II Elicits CA²⁺ Increases in A7r5 Vascular Smooth Muscle Cells. European Journal of Pharmacology. Vol.420(1). 9-18. https://doi.org/10.1016/S0014-2999(01)01004-4 PMID: 11412834 ISSN: 0014-2999