Kanwal S, Trachte G J
Department of Pharmacology, School of Medicine, University of Minnesota-Duluth.
J Pharmacol Exp Ther. 1994 Jan;268(1):117-23.
This study tested the hypothesis that neuromodulatory effects of atrial natriuretic factor (ANF) are mediated by an activation of potassium channels in the rabbit isolated vas deferens. The neuromodulatory effects of ANF were tested in the presence of the potassium channel inhibitors, tetraethylammonium, 4-aminopyridine, glibenclamide and charybdotoxin. The effects of the first three were ascertained by their prevention of neuromodulatory effects of a cromokalim enantiomer (BRL 38227), which opens ATP-sensitive potassium channels. The nonspecific potassium channel inhibitors, tetraethylammonium (2 mM) and 4-aminopyridine (2 mM) blocked inhibitory effects of both ANF and BRL 38227 on the electrically-induced adrenergic contraction in the rabbit vas deferens. Glibenclamide (10 microM), an inhibitor of ATP-sensitive potassium channels, failed to antagonize ANF effects, but blocked the actions of BRL 38227. Charybdotoxin (100 nM) is known to block large conductance calcium-activated potassium channels, and it attenuated the neuromodulatory effects of ANF; however, the effects of BRL 38227 were sustained in the presence of charybdotoxin. These results are consistent with the hypothesis that the neuromodulatory action of ANF is mediated by the activation of potassium conductances. The potassium channel involved is not an ATP-sensitive channel, because glibenclamide failed to alter the neuromodulatory activity of ANF. We hypothesize that ANF effects could be mediated by an activation of either calcium-activated or outward rectifying potassium channels.
心房利钠因子（ANF）的神经调节作用是通过激活家兔离体输精管中的钾通道来介导的。在存在钾通道抑制剂四乙铵、4-氨基吡啶、格列本脲和蝎毒素的情况下，对ANF的神经调节作用进行了测试。通过前三类抑制剂对一种可开启ATP敏感性钾通道的克罗卡林对映体（BRL 38227）的神经调节作用的抑制，来确定它们的作用效果。非特异性钾通道抑制剂四乙铵（2 mM）和4-氨基吡啶（2 mM）可阻断ANF和BRL 38227对家兔输精管电诱导的肾上腺素能收缩的抑制作用。ATP敏感性钾通道抑制剂格列本脲（10 microM）未能拮抗ANF的作用，但可阻断BRL 38227的作用。已知蝎毒素（100 nM）可阻断大电导钙激活钾通道，它可减弱ANF的神经调节作用；然而，在存在蝎毒素的情况下，BRL 38227的作用仍持续存在。这些结果与下述假说一致，即ANF的神经调节作用是由钾电导的激活所介导的。所涉及的钾通道不是ATP敏感性通道，因为格列本脲未能改变ANF的神经调节活性。我们推测，ANF的作用可能是由钙激活钾通道或外向整流钾通道的激活所介导的。
