D-Amphetamine Causes Dual Actions on Catecholamine Release from the Rat Adrenal Medulla

D-Amphetamine Causes Dual Actions on Catecholamine Release from the Rat Adrenal Medulla

The present study was designed to examine the effect of d-amphetamine on CA release from the isolated perfused model of the rat adrenal gland, and to establish its mechanism of action. D- amphetamine (10∼100μM), when perfused into an adrenal vein of the rat adrenal gland for 60 min, enhanced the CA secretory responses evoked by ACh (5.32&#8275;10<SUP>&#8291;3</SUP> M), excess K<SUP>&#8290;</SUP> (5.6&#8275;10<SUP>&#8291;2</SUP> M, a membrane depolarizer), DMPP (10<SUP>&#8291;4 </SUP>M, a selective neuronal nicotinic N<SUB>n</SUB>-receptor agonist) and McN-A-343 (10<SUP>&#8291;4 </SUP>M, a selective M<SUB>1</SUB>-muscarinic agonist) only for the first period (4 min), although it alone has weak effect on CA secretion. Moreover, d-amphetamine (30μM) in to an adrenal vein for 60 min also augmented the CA release evoked by BAY-K-8644, an activator of the dihydropyridine L-type Ca<SUP>2&#8290;</SUP> channels, and cyclopiazonic acid, an inhibitor of cytoplasmic Ca<SUP>2&#8290;</SUP> ATPase only for the first period (4 min). However, in the presence of high concentration (500μM), d-amphetamine rather inhibited the CA secretory responses evoked by the above all of secretagogues. Collectively, these experimental results suggest that d-amphetamine at low concentrations enhances the CA secretion from the rat adrenal medulla evoked by cholinergic stimulation (both nicotininc and muscarinic receptors) as well as by membrane depolarization, but at high concentration it rather inhibits them. It seems that d-amphetamine has dual effects as both agonist and antagonist at nicotinic receptors of the isolated perfused rat adrenal medulla, which might be dependent on the concentration. It is also thought that these actions of d-amphetamine are probably relevant to the Ca<SUP>2&#8290;</SUP> mobilization through the dihydropyridine L-type Ca<SUP>2&#8290;</SUP> channels located on the rat adrenomedullary chromaffin cell membrane and the release of Ca<SUP>2&#8290;</SUP> from the cytoplasmic store.