P2Y receptor-mediated enhancement of permeation requires Ca2+ signalling in vascular endothelial cells.
1. We investigated the effects of 2-methylthioATP (2meS-ATP; a P2Y receptor agonist) on the permeation of fluorescein isothiocyanate (FITC)-labelled dextran, transendothelial electrical resistance (TEER) and intracellular calcium levels ([Ca2+]i) in cultured endothelial cells isolated from the rat caudal artery. 2. The cellular transport of FITC-labelled dextran was enhanced and TEER of the endothelial monolayer was reduced by 2meS-ATP. Both these effects were prevented by pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid, a P2Y receptor antagonist, which also inhibited the increase in [Ca2+]i induced by 2meS-ATP in endothelial cells. 3. The increase in [Ca2+]i induced by 2meS-ATP was inhibited by thapsigargin (a Ca2+ pump inhibitor) and by U-73122 (a phospholipase C inhibitor). 4. These findings suggested that activation of the P2Y receptor enhances the passage of material in the endothelium, which is associated with Ca2+ signalling in endothelial cells.
Tanaka
Naoko
N
Department of Pharmacology, School of Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya 663-8179, Japan.
Kawasaki
Kumiko
K
Nejime
Namie
N
Kubota
Yoko
Y
Takahashi
Koichi
K
Hashimoto
Michio
M
Kunitomo
Masaru
M
Shinozuka
Kazumasa
K
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D058910:Purinergic P2 Receptor Agonists; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D013873:Thionucleotides / Q000494:pharmacology
D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2; D013873:Thionucleotides; D000255:Adenosine Triphosphate; C008501:2-methylthio-ATP