Decrease of acidity inside zymogen granules inhibits acetylcholine- or inositol trisphosphate-evoked cytosolic Ca2+ spiking in pancreatic acinar cells.
In isolated pancreatic acinar cells application of the proton-potassium ionophore nigericin or the proton-sodium ionophore monensin led to a reduction of acidity inside the zymogen granules which could be visualized in an imaging system by a rapid reduction in the intragranular quinacrine fluorescence. Cytosolic Ca2+ spikes in response to acetylcholine stimulation or intracellular inositol trisphosphate application were assessed by recording Ca2+ -sensitive ionic currents in the patch clamp whole-cell recording configuration. Both nigericin and monensin evoked marked reductions in frequency and amplitude of spikes and in many experiments abolished spiking altogether. The Ca2+ -sensitive membrane currents could still be activated after nigericin or monensin treatment since subsequent application of the Ca2+ ionophore ionomycin evoked a large current response. The decrease in intragranular acidity would appear to inhibit intracellular Ca2+ release perhaps due to a reduction in the free intragranular Ca2+ concentration.
Titievsky
A V
AV
MRC Secretory Control Research Group, Physiological Laboratory, University of Liverpool, Liverpool, L69 3BX, UK.
Takeo
T
T
Tepikin
A V
AV
Petersen
O H
OH
D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000187:drug effects* / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004792:Enzyme Precursors / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D015544:Inositol 1,4,5-Trisphosphate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008985:Monensin / Q000494:pharmacology; D009550:Nigericin / Q000494:pharmacology; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011796:Quinacrine; D014634:Valinomycin / Q000494:pharmacology
D004792:Enzyme Precursors; D014634:Valinomycin; D015544:Inositol 1,4,5-Trisphosphate; D008985:Monensin; D011796:Quinacrine; D000109:Acetylcholine; D009550:Nigericin; D002118:Calcium