Catecholamine secretion by chemical hypoxia in guinea-pig, but not rat, adrenal medullary cells: Differences in mitochondria

- Mitochondrial inhibitors induce secretion in chromaffin cells of guinea pigs, but not rats.
- Mitochondrial inhibitors induce a larger decrease in cellular ATP in chromaffin cells of guinea pigs, but not rats.
- The amount of F1F0-ATPase inhibitor factor in guinea-pig chromaffin cells is larger than in rat chromaffin cells.
- A large extent of reversed operation of F1F0-ATPase may be responsible for the inhibitor-induced secretion.

The effects of mitochondrial inhibitors (CN−, a complex IV inhibitor and CCCP, protonophore) on catecholamine (CA) secretion and mitochondrial function were explored functionally and biochemically in rat and guinea-pig adrenal chromaffin cells. Guinea-pig chromaffin cells conspicuously secreted CA in response to CN− or CCCP, but rat cells showed a little, if any, secretory response to either of them. The resting metabolic rates in rat adrenal medullae did not differ from those in guinea-pig adrenal medullae. On the other hand, the time course of depolarization of the mitochondrial membrane potential (ΔΨm) in guinea-pig chromaffin cells in response to CN− was slower than that in rat chromaffin cells, and this difference was abolished by oligomycin, an F1F0-ATPase inhibitor. The extent of CCCP-induced decrease in cellular ATP in guinea-pig chromaffin cells, which was indirectly measured using a Mg2+ indicator, was smaller than that in rat chromaffin cells. Relative expression levels of F1F0-ATPase inhibitor factor in guinea-pig adrenal medullae were smaller than in rat adrenal medullae, and the opposite was true for F1F0-ATPase α subunit. The present results indicate that guinea-pig chromaffin cells secrete more CA in response to a mitochondrial inhibitor than rat chromaffin cells and this higher susceptibility in the former is accounted for by a larger extent of reversed operation of F1F0-ATPase with the consequent decrease in ATP under conditions where ΔΨm is depolarized.