Metabotropic ATP receptor in hippocampal and thalamic neurones: pharmacology and modulation of Ca2+ mobilizing mechanisms.
Changes in cytoplasmic free Ca2+ concentration, [Ca]i, elicited by ATP, were studied in neurones cultured from rat hippocampus and thalamus. ATP evoked [Ca]i increases in about 30% of all cells tested and suppressed [Ca]i transients in responsive cells. The number of responses to ATP markedly increased after pretreatment of cells with inhibitors of protein kinase C, H-7 or staurosporine. The potentiation was blocked by a phorbol ester and by dioleylglycerol. In pretreated cells both once peak [Ca]i and the number of successive trials were augmented by an [ATP] increase. The former effect can be described by the Michaelis-Menten equation whereas the latter one has a steeper, leftward-shifted dependence. Both concentration dependences are explained with a model, describing Ca2+ release as a threshold phenomena. ATP analogues had the rank of potency: ATP approximately ADP >> AMP > alpha, beta-MeATP. A single ATP application depleted internal Ca2+ stores which could be replenished by brief membrane depolarization with high-K+. ATP- and caffeine-induced [Ca]i transients were independent, indicating two non-overlapping Ca2+ storage sites. Only caffeine effects were potentiated at an elevated [Ca]i level, showing a Ca(2+)-induced Ca2+ release. Inhibitors of the Ca2+ pump in internal stores, ryanodine and sulphydryl reagents suppressed the ATP-induced [Ca]i transients, acting via different mechanisms.
Mironov
S L
SL
Max-Planck-Institute for Psychiatry, Planegg-Martinsried, Germany.
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004075:Diglycerides / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D007202:Indicators and Reagents / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007700:Kinetics; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000378:metabolism*; D013788:Thalamus / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*
D004075:Diglycerides; D007202:Indicators and Reagents; D018048:Receptors, Purinergic P2; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D010727:Phosphoric Diester Hydrolases; C021491:glycerophosphoinositol glycerophosphodiesterase; D019204:GTP-Binding Proteins; D002118:Calcium