Manko 2013 Acta Physiol (Oxf)

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Manko BO, Manko VV (2013) Mechanisms of respiration intensification of rat pancreatic acini upon carbachol-induced Ca2+ release. Acta Physiol (Oxf) 208:387-99.

» PMID: 23692873

Manko BO, Manko VV (2013) Acta Physiol (Oxf)

Abstract: Acetylcholine as one of the main secretagogues modulates mitochondrial functions in acinar pancreacytes, presumably due to increase in ATP hydrolysis or Ca2+ 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.

Respiration of intact or permeabilized rat pancreatic acini was studied at 37 °C using a Clark oxygen electrode.

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.

Medium CCh dose (1 μm) intensifies respiration and oxidative phosphorylation of acinar pancreacytes by feedforward mechanism via Ca2+ transport into mitochondria and activation of Ca2+ /ADP-sensitive mitochondrial dehydrogenases. Prolonged action of high CCh dose (10 μm) might impair mitochondrial functions. Keywords: Ca2+, Carbachol, Mitochondria, Pancreatic acini, Respiration

Labels: MiParea: Respiration, mt-Medicine, mt-Awareness 

Organism: Rat  Tissue;cell: Islet cell;pancreas;thymus  Preparation: Permeabilized cells 

Regulation: Calcium  Coupling state: LEAK, OXPHOS, ET  Pathway: N, S