Kimura Kenichi, Low David A, Keller David M, Davis Scott L, Crandall Craig G
Institute for Exercise and Environmental Medicine, Presbyterian Hospital of Dallas, TX 75231, USA.
J Appl Physiol (1985). 2007 May;102(5):1856-61. doi: 10.1152/japplphysiol.01069.2006. Epub 2007 Jan 18.
The aim of this study was to evaluate cutaneous vasodilation and sweating responses to exogenous administration of acetylcholine (ACh) and methacholine (MCh), which have different sensitivities to endogenous cholinesterase. Four intradermal microdialysis probes were placed in dorsal forearm skin: two sites were perfused with ACh (1 x 10(-7)-1 M) and the other two with the same molar concentrations of MCh. Sweat rate (SR) and cutaneous blood flow were simultaneously assessed directly over each microdialysis membrane. Dose-response curves were constructed, and the effective concentration of the drug resulting in 50% of the maximal response (EC(50)) was identified. For SR and cutaneous vascular conductance (CVC), there were no significant differences in EC(50) between sites receiving the same drug: -1.52 +/- 0.18 and -1.19 +/- 0.09 log-molar concentration of ACh at distal and proximal sites, respectively, and -2.35 +/- 0.24 and -2.42 +/- 0.23 log-molar concentration of MCh at distal and proximal sites, respectively, for SR (P > 0.05) and -3.87 +/- 0.32 and -3.97 +/- 0.27 log-molar concentration of ACh at distal and proximal sites, respectively, and -4.78 +/- 0.17 and -4.46 +/- 0.16 log-molar concentration of MCh at distal and proximal sites, respectively, for CVC (P > 0.05). However, the EC(50) for CVC and SR was significantly lower at the MCh than at the ACh sites. A second procedure was performed to confirm that differences in responses between ACh and MCh could be attributed to different cholinesterase sensitivities. Similarly, four microdialysis membranes were placed in dorsal forearm skin: two sites were perfused with ACh and other two with MCh. However, one of each of the ACh and MCh sites was also perfused with 10 microM neostigmine (an acetylcholinesterase inhibitor). Neostigmine at the ACh site induced a leftward shift (i.e., lower EC(50)) of the SR and CVC dose-response curves compared with the site treated with ACh alone, resulting in no difference in the EC(50) for SR and CVC between the ACh + neostigmine and the MCh site. These results suggest that elevations in SR and CVC occur earlier with MCh than with ACh treatment because of differences in cholinesterase susceptibility between these drugs.
本研究的目的是评估皮肤血管舒张和出汗对乙酰胆碱（ACh）和醋甲胆碱（MCh）外源性给药的反应，这两种药物对内源性胆碱酯酶具有不同的敏感性。将四个皮内微透析探针置于前臂背侧皮肤：两个部位灌注ACh（1×10⁻⁷ - 1 M），另外两个部位灌注相同摩尔浓度的MCh。在每个微透析膜正上方同时直接评估出汗率（SR）和皮肤血流量。构建剂量 - 反应曲线，并确定产生最大反应50%的药物有效浓度（EC₅₀）。对于SR和皮肤血管传导率（CVC），接受相同药物的部位之间EC₅₀无显著差异：SR方面，远端和近端部位ACh的对数摩尔浓度分别为 - 1.52 ± 0.18和 - 1.19 ± 0.09，MCh的对数摩尔浓度分别为 - 2.35 ± 0.24和 - 2.42 ± 0.23（P > 0.05）；CVC方面，远端和近端部位ACh的对数摩尔浓度分别为 - 3.87 ± 0.32和 - 3.97 ± 0.27，MCh的对数摩尔浓度分别为 - 4.78 ± 0.17和 - 4.46 ± 0.16（P > 0.05）。然而，MCh部位CVC和SR的EC₅₀显著低于ACh部位。进行了第二个实验以确认ACh和MCh之间反应的差异可归因于不同的胆碱酯酶敏感性。同样，将四个微透析膜置于前臂背侧皮肤：两个部位灌注ACh，另外两个部位灌注MCh。然而，ACh和MCh部位各有一个也灌注10 μM新斯的明（一种乙酰胆碱酯酶抑制剂）。与仅用ACh处理的部位相比，ACh部位的新斯的明导致SR和CVC剂量 - 反应曲线向左移动（即较低的EC₅₀），使得ACh + 新斯的明部位和MCh部位之间SR和CVC的EC₅₀无差异。这些结果表明，由于这些药物之间胆碱酯酶敏感性的差异，MCh治疗引起的SR和CVC升高比ACh治疗更早出现。
