Doughty J M, Plane F, Langton P D
Department of Physiology, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom.
Am J Physiol. 1999 Mar;276(3):H1107-12. doi: 10.1152/ajpheart.1999.276.3.H1107.
In rat mesenteric artery, endothelium-derived hyperpolarizing factor (EDHF) is blocked by a combination of apamin and charybdotoxin (ChTX). The site of action of these toxins has not been established. We compared the effects of ChTX and apamin applied selectively to the endothelium and to the smooth muscle. In isometrically mounted arteries, ACh (0.01-10 micrometers), in the presence of indomethacin (2.8 microM) and Nomega-nitro-L-arginine methyl ester (L-NAME) (100 microM), concentration dependently relaxed phenylephrine (PE)-stimulated tone (EC50 50 nM; n = 10). Apamin (50 nM) and ChTX (50 nM) abolished this relaxation (n = 5). In pressurized arteries, ACh (10 microM), applied intraluminally in the presence of indomethacin (2.8 microM) and L-NAME (100 microM), dilated both PE-stimulated (0.3-0.5 microM; n = 5) and myogenic tone (n = 3). Apamin (50 nM ) and ChTX (50 nM) applied intraluminally abolished ACh-induced dilatations. Bath superperfusion of apamin and ChTX did not affect ACh-induced dilatations of either PE-stimulated (n = 5) or myogenic tone (n = 3). This is the first demonstration that ChTX and apamin act selectively on the endothelium to block EDHF-mediated relaxation.
在大鼠肠系膜动脉中，内皮衍生超极化因子（EDHF）可被蜂毒明肽和蝎毒素（ChTX）联合阻断。这些毒素的作用位点尚未明确。我们比较了将ChTX和蜂毒明肽分别选择性地作用于内皮和平滑肌的效果。在等长收缩的动脉中，在吲哚美辛（2.8微摩尔）和Nω-硝基-L-精氨酸甲酯（L-NAME）（100微摩尔）存在的情况下，乙酰胆碱（ACh，0.01 - 10微米）浓度依赖性地舒张苯肾上腺素（PE）刺激的张力（半数有效浓度50纳摩尔；n = 10）。蜂毒明肽（50纳摩尔）和ChTX（50纳摩尔）消除了这种舒张作用（n = 5）。在有压力的动脉中，在吲哚美辛（2.8微摩尔）和L-NAME（100微摩尔）存在的情况下，腔内应用ACh（10微米）可舒张PE刺激的张力（0.3 - 0.5微米；n = 5）和肌源性张力（n = 3）。腔内应用蜂毒明肽（50纳摩尔）和ChTX（50纳摩尔）可消除ACh诱导的舒张。浴槽中超灌注蜂毒明肽和ChTX并不影响ACh诱导的PE刺激张力（n = 5）或肌源性张力（n = 3）的舒张。这首次证明了ChTX和蜂毒明肽选择性地作用于内皮，以阻断EDHF介导的舒张。
