Influence of Tacrine on Catecholamine Secretion in the Perfused Rat Adrenal Gland
Influence of Tacrine on Catecholamine Secretion in the Perfused Rat Adrenal Gland
- Seok-Jeong Jang Won-Ho Yang Dong-Yoon Lim
- 대한생리학회-대한약리학회
- The Korean Journal of Physiology & Pharmacology
- 제6권 제4호
- 등재여부 : KCI등재
- 2002.01
- 207 - 214 (8 pages)
<P> The present study was designed to clarify whether tacrine affects the release of catecholamines (CA) from the isolated perfused model of rat adrenal gland or not and to elucidate the mechanism of its action. Tacrine (3⁓10<SUP>⁣5</SUP>∼3⁓10<SUP>⁣4 </SUP>M) perfused into an adrenal vein for 60 min inhibited CA secretory responses evoked by ACh (5.32⁓10<SUP>⁣3</SUP> M), DMPP (a selective neuronal nicotinic agonist, 10<SUP>⁣4</SUP> M for 2 min) and McN-A-343 (a selective muscarinic M<SUB>1</SUB>-agonist, 10<SUP>⁣4</SUP> M for 2 min) in relatively dose- and time- dependent manners. However, tacrine failed to affect CA secretion by high K<SUP>⁢</SUP> (5.6⁓10<SUP>⁣2</SUP> M). Tacrine itself at concentrations used in the present experiments did not also affect spontaneous CA output. Furthermore, in the presence of tacrine (10<SUP>⁣4 </SUP>M), CA secretory responses evoked by Bay-K-8644 (an activator of L-type Ca<SUP>2⁢ </SUP>channels, 10<SUP>⁣4 </SUP>M), but not by cyclopiazonic acid (an inhibitor of cytoplasmic Ca<SUP>2⁢</SUP>-ATPase, 10<SUP>⁣4 </SUP>M), was relatively time-dependently attenuated. Also, physostigmine (10<SUP>⁣4 </SUP>M), given into the adrenal gland for 60 min, depressed CA secretory responses evoked by ACh, McN-A-343 and DMPP while did not affect that evoked by high K<SUP>⁢</SUP>. Collectively, these results obtained from the present study demonstrate that tacrine greatly inhibits CA secretion from the perfused rat adrenal gland evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors, but does fail to affect that by direct membrane-depolarization. It is suggested that this inhibitory effect of tacrine may be exerted by blocking both the calcium influx into the rat adrenal medullary chromaffin cells without Ca<SUP>2⁢ </SUP>release from the cytoplasmic calcium store, that is relevant to the cholinergic blockade. Also, the mode of action between tacrine and physostigmine in rat adrenomedullary CA secretion seems to be similar.