Barro-Soria, Rene and Stindl, Julia and Mueller, Claudia and Foeckler, Renate and Todorov, Vladimir and Castrop, Hayo and Strauss, Olaf (2012) Angiotensin-2-Mediated Ca2+ Signaling in the Retinal Pigment Epithelium: Role of Angiotensin-Receptor-Associated-Protein and TRPV2 Channel. PLOS ONE, 7 (11): e49624. ISSN 1932-6203,
Full text not available from this repository. (Request a copy)Abstract
Angiotensin II (AngII) receptor (ATR) is involved in pathologic local events such as neovascularisation and inflammation including in the brain and retina. The retinal pigment epithelium (RPE) expresses ATR in its AT1R form, angiotensin-receptor-associated protein (Atrap), and transient-receptor-potential channel-V2 (TRPV2). AT1R and Atrap co-localize to the basolateral membrane of the RPE, as shown by immunostaining. Stimulation of porcine RPE (pRPE) cells by AngII results in biphasic increases in intracellular free Ca2+ inhibited by losartan. Xestospongin C (xest C) and U-73122, blockers of IP3R and PLC respectively, reduced AngII-evoked Ca2+ response. RPE cells from Atrap(-/-) mice showed smaller AngII-evoked Ca2+ peak (by 22%) and loss of sustained Ca2+ elevation compared to wild-type. The TRPV channel activator cannabidiol (CBD) at 15 mu M stimulates intracellular Ca2+-rise suggesting that porcine RPE cells express TRPV2 channels. Further evidence supporting the functional expression of TRPV2 channels comes from experiments in which 100 mu M SKF96365 (a TRPV channel inhibitor) reduced the cannabidiol-induced Ca2+-rise. Application of SKF96365 or reduction of TRPV2 expression by siRNA reduced the sustained phase of AngII-mediated Ca2+ transients by 53%. Thus systemic AngII, an effector of the local renin-angiotensin system stimulates biphasic Ca2+ transients in the RPE by releasing Ca2+ from cytosolic IP3-dependent stores and activating ATR/Atrap and TRPV2 channels to generate a sustained Ca2+ elevation.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SMOOTH-MUSCLE-CELLS; II TYPE-1 RECEPTOR; CONVERTING ENZYME; PHYSICAL STIMULI; RENIN SECRETION; CALCIUM-ENTRY; RAT RETINA; ACTIVATION; EXPRESSION; NEOVASCULARIZATION; |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Augenheilkunde Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Wolf Hayo Castrop |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 04 May 2020 06:54 |
| Last Modified: | 04 May 2020 06:54 |
| URI: | https://pred.uni-regensburg.de/id/eprint/17769 |
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