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Influence of Ketamine on Catecholamine Secretion in the Perfused Rat Adrenal Medulla  

Ko, Young-Yeob (Departments of Internal Medicine (Cardiology), College of Medicine, Chosun University)
Jeong, Yong-Hoon (Departments of Pharmacology, College of Medicine, Chosun University)
Lim, Dong-Yoon (Departments of Pharmacology, College of Medicine, Chosun University)
Publication Information
The Korean Journal of Physiology and Pharmacology / v.12, no.3, 2008 , pp. 101-109 More about this Journal
Abstract
The aim of the present study was to examine the effects of ketamine, a dissociative anesthetics, on secretion of catecholamines (CA) secretion evoked by cholinergic stimulation from the perfused model of the isolated rat adrenal gland, and to establish its mechanism of action, and to compare ketamine effect with that of thiopental sodium, which is one of intravenous barbiturate anesthetics. Ketamine ($30{\sim}300{\mu}M$), perfused into an adrenal vein for 60 min, dose- and time-dependently inhibited the CA secretory responses evoked by ACh (5.32 mM), high $K^+$ (a direct membrane-depolarizer, 56 mM), DMPP (a selective neuronal nicotinic NN receptor agonist, $100{\mu}M$) and McN-A-343 (a selective muscarinic M1 receptor agonist, $100{\mu}M$). Also, in the presence of ketamine ($100{\mu}M$), the CA secretory responses evoked by veratridine (a voltage-dependent $Na^+$ channel activator, $100{\mu}M$), Bay-K-8644 (an L-type dihydropyridine $Ca^{2+}$ channel activator, $10{\mu}M$), and cyclopiazonic acid (a cytoplasmic $Ca^{2+}$-ATPase inhibitor, $10{\mu}M$) were significantly reduced, respectively. Interestingly, thiopental sodium ($100{\mu}M$) also caused the inhibitory effects on the CA secretory responses evoked by ACh, high $K^+$, DMPP, McN-A-343, veratridine, Bay-K-8644, and cyclopiazonic acid. Collectively, these experimental results demonstrate that ketamine inhibits the CA secretion evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors and the membrane depolarization from the isolated perfused rat adrenal gland. It seems likely that the inhibitory effect of ketamine is mediated by blocking the influx of both $Ca^{2+}$ and $Na^+$ through voltage-dependent $Ca^{2+}$ and $Na^+$ channels into the rat adrenal medullary chromaffin cells as well as by inhibiting $Ca^{2+}$ release from the cytoplasmic calcium store, which are relevant to the blockade of cholinergic receptors. It is also thought that, on the basis of concentrations, ketamine causes similar inhibitory effect with thiopental in the CA secretion from the perfused rat adrenal medulla.
Keywords
Ketamine; thiopental; Catecholamine secretion; Adrenal medulla; Cholinergic receptors;
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