Edvinsson L, Falck B, Owman C
J Pharmacol Exp Ther. 1977 Jan;200(1):117-26.
A pharmacological identification and characterization of cholinergic receptors was carried out in pial arteries of cats. In one series of experiments, the middle cerebral artery was suspended in an organ bath for recording fo circular motor activity. Parasympathomimetic compounds produced either a relaxation or a contraction. The relaxation occurred at low doses (up to 10(-6) M), and the response was inhibited in a competitive manner by atropine. The mean KB value (determined with acetylcholine as agonist) was 3.85 X 10(-11) M, and the corresponding pA2 value 10.43. At higher doses, the parasympathomimetics produced a contraction. This effect, too, was inhibited in a competitive manner with atropine. The calculated mean KB value with acetylcholine as agonist was 1.12 X 10(-11) M, and pA2 was 10.07. The motor responses did not require an intact perivascular sympathetic innervation, which shows that the effects were mediated by muscarinic type of cholinergic receptors present in the smooth musculature. In another series of experiments, pial arteries were preincubated in the presence of 3H-norepinephrine, and the amount of tritium efflux was measured in a superfusion system before or during electrical field stimulation (12 V, 1 msec pulse duration, 10 Hz). The efflux was minimized by sympathetic denervation, and the effect of transmural stimulation abolished by bretylium and guanethidine, which shows that the bulk of tritium overflow during stimulation originated from the perivascular sympathetic nerves. The marked elevation of tritium efflux during stimulation was enhanced by hexamethonium, and it was inhibited by nicotine and acetylcholine, whose effects were counteracted by hexamethonium (but not by atropine). This finding indicates the presence of nicotinic type of cholinergic receptors on the perivascular adrenergic nerves, allowing inhibition of norepinephrine by acetylcholine that may be liberated from the adjacent cholinergic terminals in the autonomic nerve plexus.
在猫的软脑膜动脉中进行了胆碱能受体的药理学鉴定和特性研究。在一系列实验中，将大脑中动脉悬挂在器官浴槽中以记录其环形运动活性。拟副交感神经化合物可引起舒张或收缩。低剂量（高达10⁻⁶ M）时出现舒张，该反应被阿托品以竞争性方式抑制。以乙酰胆碱为激动剂测定的平均KB值为3.85×10⁻¹¹ M，相应的pA2值为10.43。高剂量时，拟副交感神经化合物引起收缩。这种效应也被阿托品以竞争性方式抑制。以乙酰胆碱为激动剂计算的平均KB值为1.12×10⁻¹¹ M，pA2为10.07。运动反应不需要完整的血管周围交感神经支配，这表明这些效应是由平滑肌组织中存在的毒蕈碱型胆碱能受体介导的。在另一系列实验中，将软脑膜动脉在3H-去甲肾上腺素存在下预孵育，并在电场刺激（12 V，1毫秒脉冲持续时间，10 Hz）之前或期间在灌流系统中测量氚外流的量。交感神经去支配使外流最小化，而溴苄铵和胍乙啶消除了跨壁刺激的作用，这表明刺激期间大部分氚溢出源自血管周围交感神经。六甲铵增强了刺激期间氚外流的显著升高，而尼古丁和乙酰胆碱抑制了这种升高，但六甲铵可抵消其作用（但阿托品不能）。这一发现表明血管周围肾上腺素能神经上存在烟碱型胆碱能受体，使得乙酰胆碱可抑制去甲肾上腺素，乙酰胆碱可能从自主神经丛中相邻的胆碱能终末释放出来。
