P2Y2 receptor elevates intracellular calcium concentration in rabbit eye suprachoroid.
Effects of ATP on the intracellular free calcium ion concentration ([Ca2+]i) in the rabbit eye suprachoroid were investigated by means of fura-2 microfluorophotometry. ATP application (10 to 100 microM) elicited a dose-dependent biphasic [Ca2+]i-increase: a fast phase typically peaking within 30 s and a following slow plateau phase, which lasted during the presence of ATP. The slow plateau phase was markedly diminished by removal of extracellular Ca2+, whereas the fast phase remained. An inhibitor of Ca2+ release from the sarcoplasmic reticulum (TMB-8), an endoplasmic Ca2+-ATPase inhibitor (thapsigargin) and a phospholipase C (PLC) inhibitor (U-73122) diminished the fast phase. A P2 receptor antagonist (Suramin) inhibited the ATP-induced [Ca2+]i-response. The potency order of ATP and related substances in producing the [Ca2+]i-elevation was UTP approximately equals ATP>ATP-gamma-S>ITP>ADP. beta,gamma-MethyleneATP, 2-methylthioATP and UDP evoked no response. This order is consistent with the P2Y2 receptor characteristics. Cross-desensitization between ATP and UTP excludes the co-existence of the other types of receptors. In conclusion, the ATP-induced [Ca2+]i-elevation in the rabbit eye suprachoroid was elicited by the Ca2+ release from the PLC-dependent, thapsigargin-sensitive intracellular Ca2+ storage sites by activating P2Y2 nucleotide receptors.
Sugamoto
Y
Y
Department of Ophthalmology, Faculty of Medicine, Tokyo Medical and Dental University, Japan. y.sugamoto.oph@med.tmd.ac.jp
Hirai
K
K
Tokoro
T
T
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D002829:Choroid / Q000187:drug effects / Q000378:metabolism*; D003592:Cytophotometry; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D005260:Female; D005456:Fluorescent Dyes; D016257:Fura-2; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D011817:Rabbits; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000502:physiology*; D058473:Receptors, Purinergic P2Y2; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D013223:Statistics as Topic; D013498:Suramin / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D013997:Time Factors; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors; D014544:Uridine Triphosphate / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D004963:Estrenes; D005456:Fluorescent Dyes; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D018048:Receptors, Purinergic P2; D058473:Receptors, Purinergic P2Y2; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D013498:Suramin; D005707:Gallic Acid; D019284:Thapsigargin; D000255:Adenosine Triphosphate; D010738:Type C Phospholipases; D002118:Calcium; D016257:Fura-2; D014544:Uridine Triphosphate