PT  - JOURNAL ARTICLE
AU  - Hofmann, Nicole A.
AU  - Barth, Sonja
AU  - Waldeck-Weiermair, Markus
AU  - Klec, Christiane
AU  - Strunk, Dirk
AU  - Malli, Roland
AU  - Graier, Wolfgang F.
TI  - TRPV1 mediates cellular uptake of anandamide and thus promotes endothelial cell proliferation and network-formation
AID  - 10.1242/bio.20149571
DP  - 2014 Dec 15
TA  - Biology Open
PG  - 1164--1172
VI  - 3
IP  - 12
4099  - http://bio.biologists.org/content/3/12/1164.short
4100  - http://bio.biologists.org/content/3/12/1164.full
SO  - Biology Open2014 Dec 15; 3
AB  - Anandamide (N-arachidonyl ethanolamide, AEA) is an endogenous cannabinoid that is involved in various pathological conditions, including cardiovascular diseases and tumor-angiogenesis. Herein, we tested the involvement of classical cannabinoid receptors (CBRs) and the Ca2+-channel transient receptor potential vanilloid 1 (TRPV1) on cellular AEA uptake and its effect on endothelial cell proliferation and network-formation. Uptake of the fluorescence-labeled anandamide (SKM4-45-1) was monitored in human endothelial colony-forming cells (ECFCs) and a human endothelial-vein cell line (EA.hy926). Involvement of the receptors during AEA translocation was determined by selective pharmacological inhibition (AM251, SR144528, CID16020046, SB366791) and molecular interference by TRPV1-selective siRNA-mediated knock-down and TRPV1 overexpression. We show that exclusively TRPV1 contributes essentially to AEA transport into endothelial cells in a Ca2+-independent manner. This TRPV1 function is a prerequisite for AEA-induced endothelial cell proliferation and network-formation. Our findings point to a so far unknown moonlighting function of TRPV1 as Ca2+-independent contributor/regulator of AEA uptake. We propose TRPV1 as representing a promising target for development of pharmacological therapies against AEA-triggered endothelial cell functions, including their stimulatory effect on tumor-angiogenesis.