Pituitary ATP receptors: characterization and functional localization to gonadotropes.
We have used real-time dynamic video imaging of Fura-2 fluorescence to study the acute effects of extracellular ATP on [Ca2+]i in pituitary cells and found that ATP produced a rapid biphasic cytosolic Ca2+ increase in a dose-dependent manner in both rat pituitary gonadotropes and gonadotrope-derived alpha T3-1 cells. Removal of extracellular Ca2+ only attenuated the plateau phase of ATP-induced intracellular Ca2+ response and suramin (100 microM), a P2-purinoceptor antagonist, reduced the ATP effect by 40-60%. Further studies revealed the following rank-order of agonist potency in the Ca2+ response: -ATP = ADP = UTP > 2-methylthioATP >> beta, gamma-methylene ATP/alpha,beta-methylene ATP. Both homologous and heterologous desensitization occurred with ATP and UTP and these did not have additive effects. Together the data suggest that the intracellular Ca2+ responses of gonadotropes and alpha T3-1 cells to these nucleotides are mediated by a single class of receptor pharmacologically characterized as the P2U subtype. This is the first demonstration of functional ATP receptors in pituitary gonadotropes.
Chen
Z P
ZP
Department of Medicine, University of Bristol, Bristol Royal Infirmary, UK.
Levy
A
A
McArdle
C A
CA
Lightman
S L
SL
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006062:Gonadotropins / Q000378:metabolism; D009994:Osmolar Concentration; D010902:Pituitary Gland / Q000378:metabolism*; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D013498:Suramin / Q000494:pharmacology; D014018:Tissue Distribution; D014544:Uridine Triphosphate / Q000494:pharmacology
D006062:Gonadotropins; D018048:Receptors, Purinergic P2; D013498:Suramin; D002118:Calcium; D014544:Uridine Triphosphate