Bognar I T, Wesner M T, Fuder H
Pharmakologisches Institut der Universität, Mainz, Federal Republic of Germany.
Naunyn Schmiedebergs Arch Pharmacol. 1990 Jan-Feb;341(1-2):22-9. doi: 10.1007/BF00195053.
The potencies of several muscarine receptor antagonists in blocking either the autoinhibition of acetylcholine release or the muscarinic contraction of the sphincter muscle upon acetylcholine release were investigated in the guinea-pig iris. The agonist at pre- or postjunctional muscarine receptors was acetylcholine released upon field stimulation (5.5 Hz, 2 min) of the irides preloaded with 14C-choline. The stimulation-evoked 14C-overflow was doubled in the presence of atropine 0.1 mumol/l but unaffected by the agonist (+/-)-methacholine (50 mumol/l). Thus, under the present stimulation conditions, the autoinhibition of acetylcholine release on the guinea-pig iris cholinergic nerves was nearly maximally activated. Isotonic contractions of the irides upon field stimulation consisted of a rapid, atropine (0.1 mumol/l)-sensitive peak phase followed by a sustained contraction which involved a cholinergic and a non-cholinergic stimulation of the sphincter muscle. The M2-selective antagonists methoctramine (10 mumol/l) and gallamine (100 mumol/l) increased both the 14C-overflow and the peak contractions evoked by field stimulation. In contrast, the M3-selective antagonist hexahydrosiladifenidol (0.1-10 mumol/l) failed to affect the evoked 14C-release but concentration-dependently (1-10 mumol/l) reduced the iris contractions. Pirenzepine (10 mumol/l) enhanced the evoked 14C-overflow and inhibited the peak contractions (0.1-10 mumol/l; maximal effect at 10 mumol/l). The low potency of the antagonist at both receptor sites indicates that an M1 muscarine receptor is not involved. The results are consistent with the idea of M2 muscarine receptors mediating autoinhibition of acetylcholine release in the guinea-pig iris and M3-like receptors inducing the contraction of the sphincter muscle.
在豚鼠虹膜中研究了几种毒蕈碱受体拮抗剂阻断乙酰胆碱释放的自身抑制或乙酰胆碱释放后括约肌的毒蕈碱收缩的效能。节前或节后毒蕈碱受体的激动剂是预先用14C - 胆碱加载的虹膜在电场刺激（5.5赫兹，2分钟）时释放的乙酰胆碱。在0.1微摩尔/升阿托品存在下，刺激诱发的14C溢出增加了一倍，但不受激动剂（±） - 醋甲胆碱（50微摩尔/升）的影响。因此，在目前的刺激条件下，豚鼠虹膜胆碱能神经上乙酰胆碱释放的自身抑制几乎被最大程度激活。电场刺激时虹膜的等张收缩包括一个快速的、对阿托品（0.1微摩尔/升）敏感的峰相，随后是持续收缩，这涉及括约肌的胆碱能和非胆碱能刺激。M2选择性拮抗剂甲溴东莨菪碱（10微摩尔/升）和加拉明（100微摩尔/升）增加了电场刺激诱发的14C溢出和峰收缩。相反，M3选择性拮抗剂六氢硅二苯酯（0.1 - 10微摩尔/升）未能影响诱发的14C释放，但浓度依赖性地（1 - 10微摩尔/升）降低了虹膜收缩。哌仑西平（10微摩尔/升）增强了诱发的14C溢出并抑制了峰收缩（0.1 - 10微摩尔/升；在10微摩尔/升时达到最大效应）。拮抗剂在两个受体位点的低效表明M1毒蕈碱受体不参与其中。结果与M2毒蕈碱受体介导豚鼠虹膜中乙酰胆碱释放的自身抑制以及M3样受体诱导括约肌收缩的观点一致。
