ISSN:
1432-1912
Keywords:
Noradrenaline release
;
ARL-115
;
Ouabain binding
;
Mitochondrial calcium
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary The cardiotonic pyridine derivative ARL-115 increased the spontaneous and electrically-evoked release of 3H-noradrenaline from the cat right atrium superfused with oxygenated Krebs-bicarbonate solution at 37°C. On the contrary, ouabain inhibited the evoked release while it also enhanced the spontaneous release of the transmitter. Vanadate did not affect either spontaneous or evoked release. Tetraethylammonium chloride (TEA) and 4-aminopyridine (4-AP) greatly potentiated 3H-noradrenaline release induced by electrical stimulation; when applied in addition to each agent, ARL-115 failed to further increase the secretory response. 3H-ouabain specific binding to partially purified bovine adrenal medulla plasma membranes was very efficiently antagonized by cold ouabain, but not by vanadate or ARL-115, even at concentrations as high as 10−3 mol/l. 45Ca uptake into isolated bovine adrenal medulla mitochondria was prevented by dinitrophenol (DNP) but unchanged in the presence of ARL-115. 45Ca release from preloaded mitochondria was, again, markedly increased by DNP, but not affected by ARL-115. The results suggest that ARL-115 enhances the release of noradrenaline from cardiac sympathetic nerves by a TEA- and 4-AP-like action. In this manner, ARL-115 would inactivate the K+ current in the nerve terminals, thereby prolonging the duration of the action potential, allowing the Ca2+ channels to remain open longer and more Ca2+ to enter the terminal. ARL-115 is not acting like digitalis.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00510137
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