IP(3)and cyclic ADP-ribose induced Ca(2+) release from intracellular stores of pancreatic acinar cells from rat in primary culture.
We have measured Ca(2+)concentration changes in intracellular Ca(2+)stores ([Ca(2+)](store)) of rat pancreatic acinar cells in primary culture in response to the Ca(2+)mobilizing substances inositol-1,4,5-trisphosphate (IP(3)) and cyclic ADP-ribose (cADPr) using the Ca(2+)-sensitive dye mag Fura-2. We found that in this cell model IP(3)releases Ca(2+)in a quantal manner. Higher Ca(2+)concentration in the stores allowed a response to lower IP(3)concentrations ([IP(3)]) indicating that the sensitivity of IP(3)receptors to IP(3)is regulated by the Ca(2+)concentration in the stores. Cyclic ADPr, that modifies 'Ca(2+)-induced-Ca(2+)-release' (CICR), was also able to release Ca(2+)from intracellular stores of pancreatic acinar cells in primary culture. In comparison to the Ca(2+)ionophore ionomycin, which induced a maximal decrease (100%) in [Ca(2+)](store), a hypermaximal [IP(3)] (10 microM) dropped [Ca(2+)](store)by 87% and cADPr had no further effect. Cyclic ADPr reduced [Ca(2+)](store)by only 56% and subsequent IP(3)addition caused further maximal decrease in [Ca(2+)](store). Furthermore, a maximal [IP(3)] caused the same decrease in [Ca(2+)](store)in all regions of the cell, whereas cADPr dropped the [Ca(2+)](store)between 20 and 80% in different cell regions. From these data we conclude that in primary cultured rat pancreatic acinar cells at least three types of Ca(2+)stores exist. One type possessing both cADPr receptors and IP(3)receptors, a second type possessing only IP(3)receptors, and a third type whose Ca(2+)can be released by ionomycin but neither by IP(3)nor by cADPr.
Göbel
A
A
Universität des Saarlandes, Physiologisches Institut, Homburg/Saar, Germany.
Krause
E
E
Feick
P
P
Schulz
I
I
D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D002451:Cell Compartmentation / Q000502:physiology; D002478:Cells, Cultured; D036563:Cyclic ADP-Ribose; D005456:Fluorescent Dyes; D016257:Fura-2 / Q000031:analogs & derivatives*; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology*; D010179:Pancreas / Q000166:cytology / Q000378:metabolism*; D051381:Rats
D005456:Fluorescent Dyes; D036563:Cyclic ADP-Ribose; C058776:2-(2-(5-carboxy)oxazole)-5-hydroxy-6-aminobenzofuran-N,N,O-triacetic acid; D000246:Adenosine Diphosphate Ribose; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium; D016257:Fura-2