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.

Influence of Total Ginseng Saponin on Contractile Responses of Vasoconstrictors in the Isolated Rat Aorta

BACKGROUND: It has been known that Ginseng extract causes the hypotensive action while it rather produces the hypertensive action. Some studies have suggested that Ginseng extract causes a biphasic response on blood pressure, namely, transient fall followed by prolonged elevation. It has been also shown that administration of Korean Red Ginseng powder has no effect on blood pressure in normotensive and hypertensive rats. The present study was designed to examine the effect of total Ginseng saponin on contractile responses of vasoconstrictors in the rat aorta and to establish the mechanism of its action. METHODS: The ring segment of aorta was mounted in a muscle bath filled with oxygenated Krebs solution for the measurement of isometric tension. After the equilibration period, under the presence of total Ginseng saponin, isometric tension induced by some vasoconstrictors were observed and compared to the control responses. The data were expressed as % of the control tension. RESULTS: Phenylephrine (an adrenergic alpha1-receptor agonist) and high potassium (a membrane depolarizing agent) caused greatly contractile responses in the rat aorta, respectively. However, in the presence of total ginseng saponin (600 g/ml), the contractile responses of phenylephrine (10(-6) and 10(-5) M) and high potassium (3.5 x 10(-2) and 5.6 x 10(-2) M) were markedly potentiated whereas prostglandin F2alpha(5 x 10(-6) M)-induced contractile responses was not affected. The contractile responses induced by phenylephrine (10(-5) M) and high potassium (3.5 x 10(-2) M) even under the presence of total ginseng saponin (600 g/ml) were greatly inhibited by the pretreatment of nicardipine (10(-6) M), a calcium channel blocker. CONCLUSION: Taken together, these experimental results suggest that total ginseng saponin can enhance the contractile responses evoked by stimulation of adrenergic alpha1-receptor and the membrane depolarization in the isolated rat aortic strips, which seems to be associated to calcium influx.

Mechanism of vasoactive intestinal polypeptide-induced catecholamine secretion from the rat adrenal medulla

The present study was attempted to investigate the effect of vasoactive intestinal polypeptide (VIP) on secretion of catecholamines (CA) and to establish whether there is the existence of a noncholinergic mechanism in adrenomedullary CA secretion from the isolated perfused rat adrenal gland. The perfusion into an adrenal vein of VIP (3 X 10-6 M) for 5 min or the injection of acetylcholine (ACh, 5.32 X 10-3 M) resulted in great increases in CA secretion. Tachyphylaxis to releasing effect of CA evoked by VIP was not observed by the repeated perfusion. The net increase in adrenal CA secretion evoked by VIP still remained unaffected in the presence of atropine or chlorisondamine. However, the CA release in response to ACh was greatly inhibited by the pretreatment with atropine or chlorisondamine. The releasing effects of CA evoked by either VIP or ACh were depressed by pretreatment with nicardipine, TMB-8, and the perfusion of Ca2+-free medium. Moreover, VIP- as well as ACh-evoked CA secretory responses were markedly inhibited under the presence of (Lys1, Pro2.5, Arg3.4, Tyr6)-VIP or naloxone. CA secretory responses induced by ACh and high K+ (5.6 X 10-2 M) were potentiated by infusion of VIP (3 X 10-6 M for 5 min). Taken together, these experimental results indicate that VIP causes CA release in a fashion of calcium ion-dependence, suggesting strongly that there exists a noncholinergic mechanism that may be involved in the regulation of adrenomedullary CA secretion through VIP receptors in the rat adrenal gland, and that VIP may be the noncholinergic excitatory secretagogue present in the chromaffin cells.