Naltrexone Inhibits Catecholamine Secretion Evoked by Nicotinic Receptor Stimulation in the Perfused Rat Adrenal Medulla

The purpose of the present study was to examine the effect of naltrexone, an opioid antagonist, on secretion of catecholamines (CA) evoked by cholinergic nicotinic stimulation and membrane-depolarization from the isolated perfused rat adrenal gland and to establish the mechanism of its action. Naltrexone (3x10 (-6) M) perfused into an adrenal vein for 60 min produced time-dependent inhibition in CA secretory responses evoked by ACh (5.32x10 (-3) M), high K+ (5.6x10 (-2) M), DMPP (10 (-4) M) and McN-A-343 (10 (-4) M). Naltrexone itself did also fail to affect basal CA output. In adrenal glands loaded with naltrexone (3x10 (-6) M), the CA secretory responses evoked by Bay-K-8644, an activator of L-type Ca2+ channels and cyclopiazonic acid, an inhibitor of cytoplasmic Ca2+-ATPase, were also inhibited. However, in the presence of met-enkephalin (5x10 (-6) M), a well-known opioid agonist, the CA secretory responses evoked by ACh, high K+, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid were also significantly inhibited. Collectively, these experimental results demonstrate that naltrexone inhibits greatly CA secretion evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors as well as that by membrane depolarization. It seems that this inhibitory effect of naltrexone does not involve opioid receptors, but might be mediated by blocking both the calcium influx into the rat adrenal medullary chromaffin cells and the uptake of Ca2+ into the cytoplasmic calcium store, which are at least partly relevant to the direct interaction with the nicotinic receptor itself.

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 (10~100microM), when perfused into an adrenal vein of the rat adrenal gland for 60 min, enhanced the CA secretory responses evoked by ACh (5.32x10-3 M), excess K+ (5.6x10-2 M, a membrane depolarizer), DMPP (10-4 M, a selective neuronal nicotinic Nn-receptor agonist) and McN-A-343 (10-4 M, a selective M1-muscarinic agonist) only for the first period (4 min), although it alone has weak effect on CA secretion. Moreover, d-amphetamine (30microM) 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 Ca2+ channels, and cyclopiazonic acid, an inhibitor of cytoplasmic Ca2+ ATPase only for the first period (4 min). However, in the presence of high concentration (500microM), 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 Ca2+ mobilization through the dihydropyridine L-type Ca2+ channels located on the rat adrenomedullary chromaffin cell membrane and the release of Ca2+ from the cytoplasmic store.