The aim of the present study was to examine the effects of green tea extract (CUMS6335) on the release of CA evoked by cholinergic stimulation and direct membrane-depolarization in the perfused model of the adrenal gland isolated from the spontaneously hypertensive rats (SHRs), and to establish the mechanism of action. Furthermore, it was also to test whether there is species difference between animals, and between CUMS6335 and EGCG, one of biologically the most powerful catechin compounds found in green tea. CUMS6335 (100 ug/ml), when perfused into an adrenal vein for 60 min, time-dependently inhibited the CA secretory responses evoked by ACh (5.32 mM), high K+ (56 mM), DMPP (100 uM), and McN-A-343 (100 uM) from the isolated perfused adrenal glands of SHRs. However, CUMS6335 itself did fail to affect basal catecholamine output. Also, in adrenal glands loaded with CUMS6335 (100 ug/ml), the CA secretory responses evoked by Bay-K-8644 (10 uM) and cyclopiazonic acid (10 uM) were also inhibited in a relatively time-dependent fashion. However, in the presence of EGCG (8.0 ug/ml) for 60 min, the CA secretory response evoked by ACh, high K+, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid were not affected except for last period. Collectively, these results indicate that CUMS6335 inhibits the CA secretion evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors as well as by direct membranedepolarization from the perfused adrenal gland of the SHR. It seems that this inhibitory effect of CUMS6335 is exerted by blocking both the calcium influx into the rat adrenal medullary chromaffin cells and the uptake of Ca2+ into the cytoplasmic calcium store, which are at least partly relevant to the direct interaction with the nicotinic receptor itself. It seems likely that there is much difference in mode of the CA-releasing action between CUMS6335 and EGCG.