R-(⁣)-TNPA, a Dopaminergic D<SUB>2</SUB> Receptor Agonist, Inhibits Catecholamine Release from the Rat Adrenal Medulla
R-(⁣)-TNPA, a Dopaminergic D<SUB>2</SUB> Receptor Agonist, Inhibits Catecholamine Release from the Rat Adrenal Medulla
- Soon-Pyo Hong Hong-Joo Seo Dong-Yoon Lim
- 대한생리학회-대한약리학회
- The Korean Journal of Physiology & Pharmacology
- 제10권 제5호
- 등재여부 : KCI등재
- 2006.01
- 273 - 282 (10 pages)
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 D<SUB>2</SUB> receptor and S(⁣)-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-(⁣)-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>⁢</SUP> (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 Ca<SUP>2⁢</SUP> channels and cyclopiazonic acid (10μM), an inhibitor of cytoplasmic Ca<SUP>2⁢</SUP>-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<SUP>⁢</SUP>, 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<SUP>⁢</SUP>, 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 D<SUB>2</SUB> receptors located on the rat adrenomedullary chromaffin cells, while the facilitatory effect of S(⁣)-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.