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KCI등재 학술저널

R-(&#8291;)-TNPA, a Dopaminergic D<SUB>2</SUB> Receptor Agonist, Inhibits Catecholamine Release from the Rat Adrenal Medulla

R-(&#8291;)-TNPA, a Dopaminergic D<SUB>2</SUB> Receptor Agonist, Inhibits Catecholamine Release from the Rat Adrenal Medulla

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The aim of the present study was to investigate the effects of R-(&#8291;)-2,10,11-trihydroxy-N-propylnoraporphine [R-(&#8291;)-TNPA], a selective agonist of dopaminergic D<SUB>2</SUB> receptor and S(&#8291;)-raclopride, a selective antagonist of dopaminergic D<SUB>2</SUB> 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-(&#8291;)-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<SUP>&#8290;</SUP> (56 mM), DMPP (100μM) and McN-A-343 (100μM). R-(&#8291;)-TNPA itself did also fail to affect basal CA output. Also, in adrenal glands loaded with R-(&#8291;)-TNPA (30μM), the CA secretory responses evoked by Bay-K-8644 (10μM), an activator of L-type Ca<SUP>2&#8290;</SUP> channels and cyclopiazonic acid (10μM), an inhibitor of cytoplasmic Ca<SUP>2&#8290;</SUP>-ATPase were also inhibited. However, S(&#8291;)-raclopride (1∼10μM), given into an adrenal vein for 60 min, enhanced the CA secretory responses evoked by ACh, high K<SUP>&#8290;</SUP>, DMPP and McN-A-343 only for the first period (4 min), although it alone has weak effect on CA secretion. Moreover, S(&#8291;)-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-(&#8291;)-TNPA (30μM) and S(&#8291;)-raclopride (3.0μM), the inhibitory responses of R-(&#8291;)-TNPA (30μM) on the CA secretion evoked by ACh, high K<SUP>&#8290;</SUP>, DMPP, McN-A-343, Bay-K-8644, and cyclopiazonic acid were significantly reduced. Taken together, these experimental results suggest that R-(&#8291;)-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(&#8291;)- raclopride rather enhances the CA release by them. It seems that this inhibitory of R-(&#8291;)-TNPA may be mediated by stimulation of inhibitory dopaminergic D<SUB>2</SUB> receptors located on the rat adrenomedullary chromaffin cells, while the facilitatory effect of S(&#8291;)-raclopride is due to the blockade of dopaminergic D<SUB>2</SUB> receptors, which are relevant to extra- and intracellular calcium mobilization. Therefore, it is thought that dopaminergic D<SUB>2</SUB> receptors may be involved in regulation of CA release in the rat adrenal medulla.

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