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Characterization of muscarinic receptors mediating relaxation and contraction in the rat iris dilator muscle
Author(s) -
Masuda Yutaka,
Yamahara Natsuki S.,
Tanaka Masako,
Ryang Shinwon,
Kawai Tomoyuki,
Imaizumi Yuji,
Watanabe Minora
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb13271.x
Subject(s) - methoctramine , muscarinic acetylcholine receptor , pilocarpine , endocrinology , medicine , dilator , pirenzepine , chemistry , acetylcholine , contraction (grammar) , receptor , biology , neuroscience , epilepsy
1 The characteristics of muscarinic receptors mediating relaxation and/or contraction in the rat iris dilator muscle were examined. 2 Relaxation was induced in a dilator muscle by application of acetylcholine (ACh) at low doses (3 μ m or less) and contraction was induced by high doses. Methacholine and carbachol also showed biphasic effects similar to those of ACh; in contrast, bethanechol, arecoline, pilocarpine and McN‐A‐343 induced mainly relaxation but no substantial contraction. 3 After parasympathetic denervation by ciliary ganglionectomy, the relaxant response to muscarinic agonists disappeared upon nerve stimulation. Application of McN‐A‐343 and pilocarpine induced only small contractions in denervated dilator muscles, indicating that these are partial agonists for contraction. 4 pA 2 values of pirenzepine, methoctramine, AF‐DX 116, himbacine, and 4‐DAMP for antagonism to pilocarpine‐induced relaxation in normal dilator muscles and those for antagonism to ACh‐induced contraction in denervated dilator muscles were determined. The pA 2 values for antagonism to relaxation of all these antagonists were most similar to those for M 3 ‐type muscarinic receptors. 5 Although pA 2 values for contraction of these antagonists, except for methoctramine, were very close to those for relaxation, contraction was not significantly antagonized by methoctramine. Contraction might be mediated by M 3 ‐like receptors which have a very low affinity for methoctramine. 6 In conclusion, ACh‐induced biphasic responses in rat iris dilator muscles were clearly distinguished from each other by specific muscarinic agonists and parasympathetic denervation, whereas muscarinic receptors could not be subclassified according to the pA 2 values of 5 specific antagonists only.