R-(-)-TNPA, a Dopaminergic D2 Receptor Agonist, Inhibits Catecholamine Release from the Rat Adrenal Medulla

ABSTRACT

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 (10~100 micrometer) 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 (100 micrometer) and McN-A-343 (100 micrometer). R-(-)-TNPA itself did also fail to affect basal CA output. Also, in adrenal glands loaded with R-(-)-TNPA (30 micrometer), the CA secretory responses evoked by Bay-K-8644 (10 micrometer), an activator of L-type Ca2+ channels and cyclopiazonic acid (10 micrometer), an inhibitor of cytoplasmic Ca2+-ATPase were also inhibited. However, S(-)-raclopride (1~10 micrometer), 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 (3.0 micrometer) 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 (30 micrometer) and S(-)-raclopride (3.0 micrometer), the inhibitory responses of R-(-)-TNPA (30 micrometer) 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.