2-aminoethoxydiphenyl borate inhibits agonist-induced Ca2+ signals by blocking inositol trisphosphate formation in acutely dissociated mouse pancreatic acinar cells.
Evidence suggests that 2-aminoethoxydiphenyl borate (2-APB) modulates intracellular Ca(2+) signals in a complex manner. 2-APB inhibits or potentiates intracellular Ca(2+) signals in different cell types, perhaps through different mechanisms. Here, we report a novel mechanism underlying 2-APB-induced inhibition of agonist-activated Ca(2+) oscillations in mouse pancreatic acinar cells, using patch-clamp and biochemical techniques. Pre-treatment of the cells with 100 microM 2-APB completely abolished ACh- but not inositol trisphosphate (InsP(3))-induced Ca(2+) oscillations, suggesting that the mechanism of inhibition occurs between cytoplasmic receptors and InsP(3) receptor activation. In addition, 100 microM 2-APB significantly inhibited ACh-induced phospholipase C (PLC) activation. These findings indicate that, in mouse pancreatic acinar cells, in addition to modulating InsP(3) receptors and blocking the store-operated Ca(2+) pathway, high concentrations of 2-APB also inhibit agonist-induced Ca(2+) signals by reducing InsP(3) formation.
Wu
Jie
J
Division of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013-4496, USA. jwu2@chw.edu
Takeo
Teruko
T
Suga
Sechiko
S
Kanno
Takahiro
T
Osanai
Tomohiro
T
Mikoshiba
Katsuhiko
K
Wakui
Makoto
M
D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000818:Animals; D001896:Boron Compounds / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D015544:Inositol 1,4,5-Trisphosphate / Q000037:antagonists & inhibitors; D051379:Mice; D008813:Mice, Inbred ICR; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism
D001896:Boron Compounds; D015544:Inositol 1,4,5-Trisphosphate; C109986:2-aminoethoxydiphenyl borate; D010738:Type C Phospholipases; D000109:Acetylcholine; D002118:Calcium