Effects of antimycin A on receptor-activated calcium mobilization and phosphoinositide metabolism in rat parotid gland.
The effects of the mitochondrial poison, antimycin A, on responses of parotid acinar cells to cholinergic stimuli were examined. Antimycin A (10 microM) partially inhibited the agonist-induced increase in 86Rb efflux. Specifically, the initial transient phase of the response, believed to arise from intracellular calcium release, was partially inhibited, while the sustained phase of the response, believed to result from calcium entering from the extracellular space, was completely blocked. The stimulation of 45Ca influx by a cholinergic agonist was also completely blocked. Antimycin A (10 microM) caused a rapid loss of [32P] polyphosphoinositides. Stimulation of [32P]phosphatidylinositol breakdown and [32P] phosphatidate synthesis by methacholine was blocked by antimycin A. Breakdown of [32P]phosphatidylinositol-4,5-bisphosphate in response to cholinergic stimulation was partially inhibited. These results indicated that the activation by cholinergic agonists of cellular calcium mobilization as well as effects on phosphoinositide metabolism are similarly inhibited by antimycin A. Furthermore, this presumably indicates a role for ATP in receptor-activated calcium mobilization and phosphoinositide turnover.
D000818:Animals; D000968:Antimycin A / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D007473:Ion Channels / Q000378:metabolism; D008297:Male; D016210:Methacholine Chloride; D008688:Methacholine Compounds / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology; D010306:Parotid Gland / Q000187:drug effects*; D010716:Phosphatidylinositols / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011950:Receptors, Cholinergic / Q000187:drug effects*; D011976:Receptors, Muscarinic / Q000187:drug effects; D012413:Rubidium / Q000378:metabolism
D007473:Ion Channels; D008688:Methacholine Compounds; D010277:Parasympathomimetics; D010716:Phosphatidylinositols; D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D016210:Methacholine Chloride; D000968:Antimycin A; D012413:Rubidium; D011188:Potassium; D002118:Calcium