Arecoline inhibits catecholamine release from perfused rat adrenal gland
Abstract
Aim: To study the effect of arecoline, an alkaloid isolated from Areca catechu, on
the secretion of catecholamines (CA) evoked by cholinergic agonists and the
membrane depolarizer from isolated perfused rat adrenal gland. Methods: Adrenal
glands were isolated from male Sprague-Dawley rats. The adrenal glands were
perfused with Krebs bicarbonate solution by means of a peristaltic pump. The CA
content of the perfusate was measured directly using the fluorometric method.
Results: Arecoline (0.1–1.0 mmol/L) perfused into an adrenal vein for 60 min produced
dose- and time-dependent inhibition in CA secretory responses evoked by
acetylcholine (ACh) (5.32 mmol/L), 1.1-dimethyl-4-phenyl piperazinium iodide
(DMPP) (100 μmol/L for 2 min) and 3-(m-choloro-phenyl-carbamoyl-oxy)-2-butynyl
trimethyl ammonium chloride (McN-A-343) (100 μmol/L for 2 min). However, lower
doses of arecoline did not affect CA secretion of high K+ (56 mmol/L); higher
doses greatly reduced CA secretion of high K+. Arecoline also failed to affect
basal catecholamine output. Furthermore, in adrenal glands loaded with arecoline
(0.3 mmol/L), CA secretory response evoked by Bay-K-8644 (10 μmol/L), an activator
of L-type Ca2+ channels, was markedly inhibited, whereas CA secretion by
cyclopiazonic acid (10 μmol/L), an inhibitor of cytoplasmic Ca2+-ATPase, was not
affected. Nicotine (30 μmol/L), which was perfused into the adrenal gland for 60
min, however, initially enhanced ACh-evoked CA secretory responses. As time
elapsed, these responses became more inhibited, whereas the initially enhanced
high K+-evoked CA release diminished. CA secretion evoked by DMPP and McNA-
343 was significantly depressed in the presence of nicotine. Conclusion:
Arecoline dose-dependently inhibits CA secretion from isolated perfused rat adrenal
gland evoked by activation of cholinergic receptors. At lower doses arecoline
does not inhibit CA secretion through membrane depolarization, but at larger
doses it does. This inhibitory effect of arecoline may be mediated by blocking the
calcium influx into the rat adrenal medullary chromaffin cells without the inhibition
of Ca2+ release from the cytoplasmic calcium store. There seems to be a difference
in the mode of action of nicotine and arecoline in rat adrenomedullary CA secretion.
Keywords:
the secretion of catecholamines (CA) evoked by cholinergic agonists and the
membrane depolarizer from isolated perfused rat adrenal gland. Methods: Adrenal
glands were isolated from male Sprague-Dawley rats. The adrenal glands were
perfused with Krebs bicarbonate solution by means of a peristaltic pump. The CA
content of the perfusate was measured directly using the fluorometric method.
Results: Arecoline (0.1–1.0 mmol/L) perfused into an adrenal vein for 60 min produced
dose- and time-dependent inhibition in CA secretory responses evoked by
acetylcholine (ACh) (5.32 mmol/L), 1.1-dimethyl-4-phenyl piperazinium iodide
(DMPP) (100 μmol/L for 2 min) and 3-(m-choloro-phenyl-carbamoyl-oxy)-2-butynyl
trimethyl ammonium chloride (McN-A-343) (100 μmol/L for 2 min). However, lower
doses of arecoline did not affect CA secretion of high K+ (56 mmol/L); higher
doses greatly reduced CA secretion of high K+. Arecoline also failed to affect
basal catecholamine output. Furthermore, in adrenal glands loaded with arecoline
(0.3 mmol/L), CA secretory response evoked by Bay-K-8644 (10 μmol/L), an activator
of L-type Ca2+ channels, was markedly inhibited, whereas CA secretion by
cyclopiazonic acid (10 μmol/L), an inhibitor of cytoplasmic Ca2+-ATPase, was not
affected. Nicotine (30 μmol/L), which was perfused into the adrenal gland for 60
min, however, initially enhanced ACh-evoked CA secretory responses. As time
elapsed, these responses became more inhibited, whereas the initially enhanced
high K+-evoked CA release diminished. CA secretion evoked by DMPP and McNA-
343 was significantly depressed in the presence of nicotine. Conclusion:
Arecoline dose-dependently inhibits CA secretion from isolated perfused rat adrenal
gland evoked by activation of cholinergic receptors. At lower doses arecoline
does not inhibit CA secretion through membrane depolarization, but at larger
doses it does. This inhibitory effect of arecoline may be mediated by blocking the
calcium influx into the rat adrenal medullary chromaffin cells without the inhibition
of Ca2+ release from the cytoplasmic calcium store. There seems to be a difference
in the mode of action of nicotine and arecoline in rat adrenomedullary CA secretion.