title: Mechanisms of respiration intensification of rat pancreatic acini upon carbachol-induced Ca(2+) release.
abstract: OBJECTIVE
  Acetylcholine as one of the main secretagogues modulates mitochondrial functions in acinar pancreacytes, presumably due to increase in ATP hydrolysis or Ca(2+) transport into mitochondria. The aim of this work was to investigate the mechanisms of carbachol (CCh) action on respiration and oxidative phosphorylation of isolated pancreatic acini.
  
  
  METHODS
  Respiration of intact or permeabilized rat pancreatic acini was studied at 37 °C using a Clark oxygen electrode.
  
  
  RESULTS
  Respiration rate of isolated acini in rest was 0.27 ± 0.01 nmol O2 s(-1) 10(-6) cells. Addition of 10 μM CCh into respiration chamber evoked biphasic stimulation of respiration. Rapid increase of respiration by 20.1% lasted for approx. 1 min, followed by decrease to level by 11.5% higher than control. Addition of 1 μm CCh caused monophasic increase by 11.5%. Preincubation (5 min) with 1 or 10 μm CCh elevated respiration rate by 12.5 or 11.2% respectively. FCCP prevented the effect of CCh. Preincubation with 1 (but not 10) μm CCh increased FCCP-uncoupled respiration rate. Thapsigargin slightly elevated respiration, but ryanodine did not. Application of 2-aminoethoxydiphenyl borate or ruthenium red prevented the effects of CCh on respiration, while oligomycin abolished them. Preincubation with 1 μm CCh prior to cell permeabilization increased respiration rate at pyruvate+malate oxidation, but not at succinate oxidation. In contrast, preincubation with 10 μm CCh decreased pyruvate+malate oxidation.
  
  
  CONCLUSIONS
  Medium CCh dose (1 μm) intensifies respiration and oxidative phosphorylation of acinar pancreacytes by feedforward mechanism via Ca(2+) transport into mitochondria and activation of Ca(2+) /ADP-sensitive mitochondrial dehydrogenases. Prolonged action of high CCh dose (10 μm) might impair mitochondrial functions.
authors.affiliation: Biology faculty, Department of Human and Animal Physiology Hrushevsky, Ivan Franko National university of Lviv, Lviv, Ukraine. mankobo@gmail.com
authors.forename: B O
authors.initials: BO
authors.lastname: Manko
authors.forename: V V
authors.initials: VV
authors.lastname: Manko
mesh_terms: D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology*; D002952:Citric Acid Cycle / Q000502:physiology; D008297:Male; D010101:Oxygen Consumption / Q000502:physiology*; D010179:Pancreas / Q000378:metabolism*; D051381:Rats
chemical_list: D002217:Carbachol; D002118:Calcium
keywords: Ca2+; carbachol; mitochondria; pancreatic acini; respiration