Roles of dopaminergic d(1) and d(2) receptors in catecholamine release from the rat adrenal medulla.
The aim of the present study was designed to establish comparatively the inhibitory effects of D(1)-like and D(2)-like dopaminergic receptor agonists, SKF81297 and R(-)-TNPA on the release of catecholamines (CA) evoked by cholinergic stimulation and membrane depolarization from the isolated perfused model of the rat adrenal medulla. SKF81297 (30microM) and R-(-)-TNPA (30microM) perfused into an adrenal vein for 60 min, produced great inhibition in the CA secretory responses evoked by ACh (5.32x10(- 3) M), DMPP (10(-4) M), McN-A-343 (10(-4) M), high K(+) (5.6x10(-2) M), Bay-K-8644 (10microM), and cyclopiazonic acid (10microM), respectively. For the release of CA evoked by ACh, high K(+), DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid, the following rank order of inhibitory potency was obtained: SKF81297>R-(-)-TNPA. However, R(+)-SCH23390, a selectve D(1)-like dopaminergic receptor antagonist, and S(-)-raclopride, a selectve D(2)-like dopaminergic receptor antagonist, enhanced the CA secretory responses evoked by ACh, high K(+), DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid only for 0~4 min. The rank order for the enhancement of CA release evoked by high K(+), McN-A-343 and cyclopiazonic acid was R(+)-SCH23390>S(-)-raclopride. Also, the rank order for ACh, DMPP and Bay-K-8644 was S(-)-raclopride > R(+)-SCH23390. Taken together, these results demonstrate that both SKF81297 and R-(-)-TNPA inhibit the CA release evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors and the membrane depolarization from the isolated perfused rat adrenal gland without affecting the basal release, respectively, but both R(+)-SCH23390 and S(-)-raclopride facilitate the CA release evoked by them. It seems likely that the inhibitory effects of SKF81297 and R-(-)-TNPA are mediated by the activation of D(1)-like and D(2)-like dopaminergic receptors located on the rat adrenomedullary chromaffin cells, respectively, whereas the facilitatory effects of R(+)-SCH23390 and S(-)-raclopride are mediated by the blockade of D(1)-like and D(2)-like dopaminergic receptors, respectively: this action is possibly associated with extra- and intracellular calcium mobilization. Based on these results, it is thought that the presence of dopaminergic D(1) receptors may play an important role in regulation of the rat adrenomedullary CA secretion, in addition to well-known dopaminergic D(2) receptors.
Department of Pharmacology, College of Medicine, Chosun University, Gwangju 501-759, Korea.
Young Joo
YJ
Baek
Yoo Seong
YS
Seo
Dong Yoon
DY
Lim