Korean J Physiol Pharmacol.  2008 Jun;12(3):101-109. 10.4196/kjpp.2008.12.3.101.

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

• Ko YY
• Jeong YH
• Lim DY

• KMID: 2285350
• DOI: http://doi.org/10.4196/kjpp.2008.12.3.101

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 (30~300 micrometer), 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 micrometer) and McN-A-343 (a selective muscarinic M1 receptor agonist, 100 micrometer). Also, in the presence of ketamine (100 micrometer), the CA secretory responses evoked by veratridine (a voltage-dependent Na+ channel activator, 100 micrometer), Bay-K-8644 (an L-type dihydropyridine Ca2+ channel activator, 10 micrometer), and cyclopiazonic acid (a cytoplasmic Ca2+-ATPase inhibitor, 10 micrometer) were significantly reduced, respectively. Interestingly, thiopental sodium (100 micrometer) 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 Ca2+ and Na+ through voltage-dependent Ca2+ and Na+ channels into the rat adrenal medullary chromaffin cells as well as by inhibiting Ca2+ 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.

Keyword

Ketamine; thiopental; Catecholamine secretion; Adrenal medulla; Cholinergic receptors

MeSH Terms

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
Adrenal Glands
Adrenal Medulla
Anesthetics
Anesthetics, Dissociative
Animals
Barbiturates
Calcium
Catecholamines
Chromaffin Cells
Cytoplasm
Dihydropyridines
Dimethylphenylpiperazinium Iodide
Indoles
Ketamine
Membranes
Neurons
Rats
Receptor, Muscarinic M1
Receptors, Cholinergic
Thiopental
Veins
Veratridine
(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
Anesthetics
Anesthetics, Dissociative
Barbiturates
Calcium
Catecholamines
Dihydropyridines
Dimethylphenylpiperazinium Iodide
Indoles
Ketamine
Receptor, Muscarinic M1
Receptors, Cholinergic
Thiopental
Veratridine