Partial inhibition of SERCA is responsible for extracellular Ca2+ dependence of AlF-4-induced [Ca2+]i oscillations in rat pancreatic.
AlF4-is known to generate oscillations in intracellular Ca2+ concentration ([Ca2+]i) by activating G proteins in many cell types. However, in rat pancreatic acinar cells, AlF4--evoked [Ca2+]i oscillations were reported to be dependent on extracellular Ca2+, which contrasts with the [Ca2+]i oscillations induced by cholecystokinin (CCK). Therefore, we investigated the mechanisms by which AlF4- generates extracellular Ca2+-dependent [Ca2+]i oscillations in rat pancreatic acinar cells. AlF4(-)-induced [Ca2+]i oscillations were stopped rapidly by the removal of extracellular Ca2+ and were abolished on the addition of 20 mM caffeine and 2 microM thapsigargin, indicating that Ca2+ influx plays a crucial role in maintenance of the oscillations and that an inositol 1,4,5-trisphosphate-sensitive Ca2+ store is also required. The amount of Ca2+ in the intracellular Ca2+ store was decreased as the AlF4--induced [Ca2+]i oscillations continued. Measurement of 45Ca2+ influx into isolated microsomes revealed that AlF4-directly inhibited sarco/endoplasmic reticulum Ca2+-ATPase (SERCA). The activity of plasma membrane Ca2+-ATPase during AlF4- stimulation was not significantly different from that during CCK stimulation. After partial inhibition of SERCA with 1 nM thapsigargin, 20 pM CCK-evoked [Ca2+]i oscillations were dependent on extracellular Ca2+. This study shows that AlF4- induces [Ca2+]i oscillations, probably by inositol 1,4,5-trisphosphate production via G protein activation but that these oscillations are strongly dependent on extracellular Ca2+ as a result of the partial inhibition of SERCA.
Chong
Seon Ah
SA
Department of Oral Biology, Yonsei University College of Dentistry, Shinchon-dong 134, Seodaemun-gu, Seoul 120-752, Korea.
Hong
Soo Young
SY
Moon
Seok Jun
SJ
Park
Jee Won
JW
Hong
Jeong-Hee
JH
An
Jeong Mi
JM
Lee
Syng-Ill
SI
Shin
Dong Min
DM
Seo
Jeong Taeg
JT
D017607:Aluminum Compounds / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000502:physiology*; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors* / Q000502:physiology*; D045604:Extracellular Fluid / Q000187:drug effects / Q000201:enzymology; D005459:Fluorides / Q000494:pharmacology*; D008297:Male; D010179:Pancreas / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases
D017607:Aluminum Compounds; C050992:tetrafluoroaluminate; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D005459:Fluorides; D002118:Calcium