Alonso M J, Arribas S, Marín J, Balfagón G, Salaices M
Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma, Madrid, Spain.
Brain Res. 1991 Dec 13;567(1):76-82. doi: 10.1016/0006-8993(91)91438-7.
The muscarinic (M) receptors involved in the vasodilation elicited by acetylcholine (ACh) and in the carbachol inhibition in electrically induced [3H]noradrenaline (NA) release in cat cerebral arteries was investigated. For this, atropine, pirenzepine, AF-DX 116, 4-DAMP, non-specific, M1, M2 and M3 receptor antagonists, respectively, were used. ACh elicited concentration-dependent relaxations up to 10(-6) M which were attenuated by these antagonists; the order of potency (pA2 values) to inhibit the ACh-induced relaxation was: atropine (10.1) 4-DAMP (8.9) greater than pirenzepine (7.6) greater than AF-DX 116 (5.9). The electrical stimulation (200 mA, 0.3 ms, 2 Hz, during 1 min) of these arteries preincubated with [3H]NA caused tritium release which was inhibited by carbachol (10(-6) M). The 4 antagonists attenuated the action of the M agonist; the order of potency (pIC50 values) was: atropine (8.7) greater than 4-DAMP (8.1) greater than AF-DX 116 (7.9) greater than pirenzepine (5.8). The action of McN-A-343, a putative M1 agonist, was also investigated. This agent produced small vasodilator responses and elevated concentrations (5 x 10(-5) M) inhibited the stimulated NA release, which was partially antagonized by atropine (10(-7) M) and pirenzepine (10(-8) and 10(-7) M). These results suggest the existence of M3 and M2 receptors mediating the relaxation induced by ACh and the NA release inhibition evoked by carbachol, respectively.
研究了参与乙酰胆碱（ACh）引起的血管舒张以及卡巴胆碱对猫脑动脉电诱导的[3H]去甲肾上腺素（NA）释放抑制作用的毒蕈碱（M）受体。为此，分别使用了阿托品、哌仑西平、AF-DX 116、4-二甲基氨基吡啶（4-DAMP）等非特异性、M1、M2和M3受体拮抗剂。ACh在浓度高达10^(-6) M时引起浓度依赖性舒张，这些拮抗剂可减弱这种舒张作用；抑制ACh诱导舒张的效力顺序（pA2值）为：阿托品（10.1）＞4-DAMP（8.9）＞哌仑西平（7.6）＞AF-DX 116（5.9）。对预先用[3H]NA孵育的这些动脉进行电刺激（200 mA，0.3 ms，2 Hz，持续1分钟）会导致氚释放，卡巴胆碱（10^(-6) M）可抑制这种释放。这4种拮抗剂减弱了M激动剂的作用；效力顺序（pIC50值）为：阿托品（8.7）＞4-DAMP（8.1）＞AF-DX 116（7.9）＞哌仑西平（5.8）。还研究了一种假定的M1激动剂 McN-A-343 的作用。该药物产生较小的血管舒张反应，高浓度（5×10^(-5) M）时可抑制刺激的NA释放，阿托品（10^(-7) M）和哌仑西平（10^(-8)和10^(-7) M）可部分拮抗这种作用。这些结果表明分别存在介导ACh诱导舒张和卡巴胆碱引起的NA释放抑制的M3和M2受体。
