ATP, thapsigargin and cAMP increase Ca2+ in rat hepatocytes by activating three different Ca2+ influx pathways.
The intracellular Ca2+ concentration ([Ca2+]i) in single isolated rat hepatocytes was measured using fura-2. Extracellular ATP induced La(3+)-sensitive and verapamil-insensitive Ca2+ influx together with Ca2+ release from intracellular Ca2+ stores. Incubation of hepatocytes with 2 microM thapsigargin produced a large prolonged increase in [Ca2+]i, which was insensitive to both 100 microM La3+ and 40 microM verapamil. Incubation with 1 mM dibutyryl cAMP increased [Ca2+]i in the presence of extracellular Ca2+ but did not in the absence of extracellular Ca2+, indicating that dibutyryl cAMP induces Ca2+ influx which was found to be sensitive to both La3+ and verapamil, without mobilizing Ca2+ from the intracellular pools. This study shows the presence of at least 3 different Ca2+ influx pathways in the plasma membrane: that is, 1) the ATP-induced, La(3+)-sensitive and verapamil-insensitive pathway; 2) the thapsigargin-induced, La(3+)-insensitive and verapamil-insensitive pathway; and 3) the cAMP-induced, La(3+)-sensitive and verapamil-sensitive pathway.
Ikari
A
A
Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
Sakai
H
H
Takeguchi
N
N
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D016257:Fura-2 / Q000737:chemistry; D066298:In Vitro Techniques; D007811:Lanthanum / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D019284:Thapsigargin / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004791:Enzyme Inhibitors; D003994:Bucladesine; D019284:Thapsigargin; D007811:Lanthanum; D000255:Adenosine Triphosphate; D014700:Verapamil; D002118:Calcium; D016257:Fura-2