Influence of pentobarbital-Na on stimulation-evoked catecholamine secretion in the perfused rat adrenal gland.

OBJECTIVES

The present study was attempted to investigate the effects of pentobarbital-Na, one of the barbiturates which are known to depress excitatory synaptic transmission in the central nervous system at concentrations similar to those required for the induction and maintenance of anesthesia, on catecholamines (CA) secretion evoked by cholinergic stimulation and membrane-depolarization from the isolated perfused rat adrenal gland, and to clarify the mechanism of its action.

METHODS

Mature male Sprague-Dawley rats were anesthetized with thiopenal-Na (40 mg/kg, s.c.). The adrenal gland was isolated by the methods of Wakade. A cannula used for perfusion of the adrenal gland was inserted into the distal end of the renal vein. The adrenal gland was carefully removed from the animal and placed on a platform of a leucite chamber.

RESULTS

The perfusion of pentobarbital-Na(30-300 uM) into an adrenal vein for 20 min produced relatively dose-dependent inhibition in CA secretion evoked by ACh(5.32 mM), DMPP(100 uM for 1 min), McN-A-343(200 uM for 2 min), Bay-K-8644(10 uM) and high potassium(56 mM), while it did not affect the CA secretion of cyclopiazonic acid(10 uM). Also, in the presence of thiopental-Na (100 uM), CA secretory responses evoked by ACh, DMPP, McN-A-343 and high K+ were markedly depressed. Moreover, in adrenal glands preloaded with ketamine(100 uM for 20 min), which is known to be a dissociative anesthetic, CA secretion evoked by ACh, DMPP, McN-A-343 and high K+ were significantly attenuated.

CONCLUSION

Taken together, these experimental results suggest that pentobarbital-Na depresses CA release evoked by both cholinergic stimulation and membrane-depolarization from the isolated rat adrenal medulla and that this inhibitory activity may be due to the result of the direct inhibition of Ca++ influx into the chromaffin cells without any effect on the calcium mobilization from the intracellular store.