Summary
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 μmol/l but unaffected by the agonist (±)-methacholine (50 μmol/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 μmol/l). 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 μmol/l) and gallamine (100 µmol/l). increased both the 14Goverflow and the peak contractions evoked by field stimulation. In contrast, the M3-selective antagonist hexahydrosiladifenidol (0.1–10 μmol/l) failed to affect the evoked 14C-release but concentration-dependently (1–10 μmol/l) reduced the iris contractions. Pirenzepine (10 μmol/l) enhanced the evoked 14C-overflow and inhibited the peak contractions (0.1–10 μmol/l; maximal effect at 10 μmol/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.
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Bognar, I.T., Wesner, M.T. & Fuder, H. Muscarine receptor types mediating autoinhibition of acetylcholine release and sphincter contraction in the guinea-pig iris. Naunyn-Schmiedeberg's Arch Pharmacol 341, 22–29 (1990). https://doi.org/10.1007/BF00195053
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DOI: https://doi.org/10.1007/BF00195053