The aim of the present study was to investigate the effects of R-(⁣)-2,10,11-trihydroxy-N-propylnoraporphine [R-(⁣)-TNPA], a selective agonist of dopaminergic D2 receptor and S(⁣)-raclopride, a selective antagonist of dopaminergic D2 receptor, on the secretion of catecholamines (CA) evoked by cholinergic stimulation and membrane-depolarization in the isolated perfused model of the rat adrenal gland, and also to establish its mechanism of action. R-(⁣)-TNPA (10∼100μM) perfused into an adrenal vein for 60 min produced dose- and time-dependent inhibition in CA secretory responses evoked by ACh (5.32 mM), high K⁢ (56 mM), DMPP (100μM) and McN-A-343 (100μM). R-(⁣)-TNPA itself did also fail to affect basal CA output. Also, in adrenal glands loaded with R-(⁣)-TNPA (30μM), the CA secretory responses evoked by Bay-K-8644 (10μM), an activator of L-type Ca2⁢ channels and cyclopiazonic acid (10μM), an inhibitor of cytoplasmic Ca2⁢-ATPase were also inhibited. However, S(⁣)-raclopride (1∼10μM), given into an adrenal vein for 60 min, enhanced the CA secretory responses evoked by ACh, high K⁢, DMPP and McN-A-343 only for the first period (4 min), although it alone has weak effect on CA secretion. Moreover, S(⁣)-raclopride (3.0μM) in to an adrenal vein for 60 min also augmented the CA release evoked by BAY-K-8644 and cyclopiazonic acid only for the first period (4 min). However, after simultaneous perfusion of R-(⁣)-TNPA (30μM) and S(⁣)-raclopride (3.0μM), the inhibitory responses of R-(⁣)-TNPA (30μM) on the CA secretion evoked by ACh, high K⁢, DMPP, McN-A-343, Bay-K-8644, and cyclopiazonic acid were significantly reduced. Taken together, these experimental results suggest that R-(⁣)-TNPA greatly inhibits the CA secretion from the perfused rat adrenal medulla evoked by cholinergic stimulation (both nicotininc and muscarinic receptors) and membrane depolarization, but S(⁣)- raclopride rather enhances the CA release by them. It seems that this inhibitory of R-(⁣)-TNPA may be mediated by stimulation of inhibitory dopaminergic D2 receptors located on the rat adrenomedullary chromaffin cells, while the facilitatory effect of S(⁣)-raclopride is due to the blockade of dopaminergic D2 receptors, which are relevant to extra- and intracellular calcium mobilization. Therefore, it is thought that dopaminergic D2 receptors may be involved in regulation of CA release in the rat adrenal medulla.