Modulation of Ca2+ influx dependent on store depletion by intracellular adenine-guanine nucleotide levels.
The effects of a number of metabolic inhibitors on the influx of Ca2+ activated by stimulation of receptors coupled to inositol 1,4,5-trisphosphate generation or by depletion of intracellular Ca2+ stores with thapsigargin were investigated in four different cell types: Ehrlich ascites tumor cells, Jurkat and HeLa cell lines, and rat hepatocytes. Independently of their chemical structure and site of inhibition, all of these metabolic poisons markedly inhibited Ca2+ influx without significantly affecting Ca2+ release. This inhibition was not due to membrane potential depolarization or to alteration in cytosolic pH but appeared correlated to a drop in the cellular concentration of ATP. The decreases in cellular [ATP] were paralleled by decreases in [GTP] and by increases in [ADP] and [GDP]. The reduction in ATP level necessary to drastically reduce Ca2+ influx was quite small, e.g. a 50% inhibition for a 5% reduction in [ATP], thus within the range of fluctuation presumably occurring under physiological conditions. We suggest that changes in the adenine or guanine nucleotide concentrations may represent an important modulatory mechanism of Ca2+ influx activated by store depletion.
Gamberucci
A
A
Institute of General Pathology, University of Siena, Italy.
Innocenti
B
B
Fulceri
R
R
Bànhegyi
G
G
Giunti
R
R
Pozzan
T
T
Benedetti
A
A
D000227:Adenine Nucleotides / Q000378:metabolism*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D002460:Cell Line; D005947:Glucose / Q000494:pharmacology; D006150:Guanine Nucleotides / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008297:Male; D008345:Manganese / Q000378:metabolism; D051379:Mice; D009840:Oligomycins / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012402:Rotenone / Q000494:pharmacology; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin; D014667:Vasopressins / Q000494:pharmacology
D000227:Adenine Nucleotides; D006150:Guanine Nucleotides; D009840:Oligomycins; D010835:Phytohemagglutinins; D013729:Terpenes; D012402:Rotenone; D014667:Vasopressins; D008345:Manganese; D019284:Thapsigargin; D006632:Histamine; D015544:Inositol 1,4,5-Trisphosphate; D000252:Calcium-Transporting ATPases; D005947:Glucose; D001920:Bradykinin; D002118:Calcium