Influence of SKF81297 on Catecholamine Release from the Perfused Rat Adrenal Medulla

ABSTRACT

The aim of the present study was to investigate the effects of 6-chloro-7,8-dihydroxy-1-phenyl-2,3, 4,5-tetrahydro-1H-3-benzazepine (SKF81297), a selective agonist of dopaminergic D1 receptor, on the secretion of catecholamines (CA) evoked by cholinergic stimulation and membrane-depolarization in the isolated perfused rat adrenal gland, and also to elucidate the mechanism involved. SKF81297 (10~100microM) perfused into an adrenal vein for 60 min produced dose- and time-dependent inhibition of CA secretory responses evoked by ACh (5.32 mM), high K+ (56 mM), DMPP (100microM) and McN-A-343 (100microM). Also, in adrenal glands loaded with SKF81297 (30microM), the CA secretory responses evoked by Bay-K-8644 (10microM), an activator of L-type Ca2+ channels and cyclopiazonic acid (10microM), an inhibitor of cytoplasmic Ca2+-ATPase were also inhibited. However, in the presence of the dopamine D1 receptor antagonist, (R)-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-benzazepine-7-ol (SCH23390, 3microM), which is a selective antagonist of dopaminergic D1 receptor, the inhibitory responses of SKF81297 (30microM) on the CA secretion evoked by ACh, high K+, DMPP, McN-A-343, Bay-K-8644, and cyclopiazonic acid were significantly reduced. Collectively, these experimental results suggest that SKF81297 inhibits the CA secretion from the rat adrenal medulla evoked by cholinergic stimulation (both nicotininc and muscarinic receptors) and membrane depolarization. This inhibitory of SKF81297 seems to be mediated by stimulation of dopaminergic D1 receptors located on the rat adrenomedullary chromaffin cells, which are relevant to extra- and intracellular calcium mobilization. Therefore, it is thought that the presence of the dopaminergic D1 receptors may be involved in regulation of CA release in the rat adrenal medulla.