Hicks P E, Langer S Z, Macrae A D
Br J Pharmacol. 1985 Sep;86(1):141-50. doi: 10.1111/j.1476-5381.1985.tb09444.x.
The prejunctional inhibitory effects of clonidine and 6-fluoronoradrenaline (6-FNA) have been evaluated in the isolated prostatic segment of the rat vas deferens, against the twitch response evoked by low frequency (0.1 Hz) field stimulation. The inhibitory potency of 6FNA was significantly increased in the presence of cocaine (1 microM) or pargyline (10 microM), but was not modified in the vas deferens from rats pretreated with reserpine when the endogenous levels of noradrenaline (NA) were decreased by 97%. Clonidine was significantly more potent than 6-FNA as an inhibitory agonist, and the potency of clonidine was not modified after cocaine, pargyline or reserpine. The alpha 2-adrenoceptor blocking agent idazoxan, was a competitive antagonist against the inhibitory effects of clonidine under all experimental conditions. In contrast, the only antagonism shown by idazoxan against the inhibitory effects of 6-FNA was in the presence of cocaine (1 microM), and this antagonist effect of idazoxan was not concentration-related. Low concentrations of 6-FNA caused concentration-dependent facilitatory effects on the twitch response, which were significantly greater after treatment with idazoxan (1 microM) in reserpine-treated vas deferens. These facilitatory effects of 6-FNA were always observed in the presence of prazosin (300 nM) and also after treatment of the preparations with phenoxybenzamine (10 microM), a concentration which abolished the inhibitory actions of both clonidine and 6-FNA. The facilitatory effects on the twitch response induced by low concentrations of 6-FNA are therefore unlikely to be due to either alpha 1- or alpha 2-adrenoceptor stimulation. In conclusion, the failure of idazoxan to block the inhibitory effects of 6-FNA, while exerting a potent competitive antagonism of clonidine-induced inhibitory effects, supports the proposal that alpha 2-adrenoceptors may in fact be subdivided into two subclasses, involving imidazoline and phenylethylamine recognition sites.
已在大鼠输精管的离体前列腺段中评估了可乐定和6-氟去甲肾上腺素（6-FNA）的节前抑制作用，以对抗低频（0.1Hz）场刺激诱发的抽搐反应。在可卡因（1μM）或帕吉林（10μM）存在的情况下，6FNA的抑制效力显著增加，但在用利血平预处理的大鼠输精管中，当去甲肾上腺素（NA）的内源性水平降低97%时，其抑制效力未改变。作为抑制性激动剂，可乐定的效力显著高于6-FNA，且可乐定的效力在使用可卡因、帕吉林或利血平后未改变。α2-肾上腺素能受体阻断剂咪唑克生在所有实验条件下均是可乐定抑制作用的竞争性拮抗剂。相比之下，咪唑克生对6-FNA抑制作用的唯一拮抗作用仅在可卡因（1μM）存在时出现，且咪唑克生的这种拮抗作用与浓度无关。低浓度的6-FNA对抽搐反应产生浓度依赖性的促进作用，在用利血平处理的输精管中，经咪唑克生（1μM）处理后这种促进作用显著增强。6-FNA的这些促进作用总是在哌唑嗪（300nM）存在时观察到，在用苯氧苄胺（10μM）处理制剂后也观察到，该浓度可消除可乐定和6-FNA的抑制作用。因此，低浓度6-FNA对抽搐反应的促进作用不太可能是由于α1-或α2-肾上腺素能受体刺激所致。总之，咪唑克生未能阻断6-FNA的抑制作用，而对可乐定诱导的抑制作用发挥强大的竞争性拮抗作用，这支持了α2-肾上腺素能受体实际上可能分为两个亚类的观点，这两个亚类涉及咪唑啉和苯乙胺识别位点。
