Muscarine receptor types mediating autoinhibition of acetylcholine release and sphincter contraction in the guinea-pig iris

Bognar, Irene T.; Wesner, M. T.; Fuder, H.

doi:10.1007/bf00195053

Cited by 24 publications

(12 citation statements)

References 24 publications

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“…Firstly, low concentrations of the M2-selective antagonists methoctramine, AF-DX 116 and AQ-RA 741 increased the contractile response to electrical stirtulation, presumably due to selective facilitation of acetylcholine release. A similar enhancement of cholinergic neurotransmission through selective blockade of prejunctional muscarinic receptors by methoctramine has also been observed on the sphincter muscle of guinea-pig iris (Bognar et al, 1990). Secondly, AQ-RA 741, AF-DX 116 and methoctramine were 20-200 times more potent at pre-than at postjunctional receptors.…”

Section: Characterization Of the Prejunctional Muscarinic Receptorsupporting

confidence: 64%

Characterization of prejunctional muscarinic autoreceptors in the guinea‐pig trachea

Kilbinger

Schneider

Siefken

et al. 1991

British J Pharmacology

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1 The effects of ten muscarinic antagonists on electrically evoked [3H]-acetylcholine release and muscle contraction were compared in an epithelium-free preparation of the guinea-pig trachea that had been preincubated with [3H]-choline. 2 The M3-selective antagonists UH-AH 37, 4-diphenyl-acetoxy-N-piperidine methobromide and parafluorohexahydrosiladiphenidol were more potent in reducing the contractile response than in facilitating the evoked [3H]-acetylcholine release. Hexahydrosiladiphenidol did not discriminate between pre-and postjunctional effects. The rank order of the postjunctional potencies of the ten antagonists as well as the postjunctional pA2 values obtained for hexahydrosiladiphenidol (7.95) and AQ-RA 741 (7.08) identified the muscular receptor as an M3 subtype. 3 The M2-selective antagonists methoctramine, AF-DX 116 and AQ-RA 741 were more potent in facilitating the evoked [3H]-acetylcholine release than in inhibiting the contractile response. The increase in release by low concentrations of methoctramine, AF-DX 116 and AQ-RA 741 was paralleled by an enhancement of the stimulation-evoked contractions.4 Comparison of the pre-and postjunctional potencies of the Ml-, M2-and M3-selective antagonists suggests that autoinhibition of acetylcholine release is mediated via an 'M2-like' receptor which differs from the cardiac type M2 receptor in its relatively high affinity for hexahydrosiladiphenidol.

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Section: Characterization Of the Prejunctional Muscarinic Receptorsupporting

confidence: 64%

Characterization of prejunctional muscarinic autoreceptors in the guinea‐pig trachea

Kilbinger

Schneider

Siefken

et al. 1991

British J Pharmacology

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“…The muscarinic receptor subtype predominant in iris sphincter muscles of the guinea-pig (Bognar et al, 1990) and the rabbit has been pharmacologically characterized as the M3 type by use of antagonists, whereas the presynaptic muscarinic receptors involved in autoinhibition of ACh release from nerve endings are the M2 type (Bognar et al, 1989). The finding that pilocarpine and McN-A-343, which do not activate phospholipase C (Leiber et at., 1990;Eglen et al, 1993), did not elicit contraction in sphincter muscles or in dilator muscles suggests that the receptor subtype mediating contraction may be common in dilator and sphincter muscles of the rat.…”

Section: Discussionmentioning

confidence: 99%

Characterization of muscarinic receptors mediating relaxation and contraction in the rat iris dilator muscle

Masuda

Yamahara

Tanaka

et al. 1995

British J Pharmacology

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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 gM 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 pA2 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 pA2 values for antagonism to relaxation of all these antagonists were most similar to those for M3-type muscarinic receptors. 5 Although pA2 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 M3-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 pA2 values of 5 specific antagonists only.

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“…These studies have not always yielded uniform and unambiguous results. Several studies suggested that the inhibitory autoreceptors are M 2 in the rat heart (Bognar et al 1990a) and trachea (Aas and Maclagan 1990), the guinea-pig iris (Bognar et al 1990b), the rabbit urinary bladder Sjögren 1995, 1998) and the human heart (Oberhauser et al 2001). On the other hand it has been proposed that the inhibitory autoreceptors are M 1 in the chicken heart (Brehm et al 1992) and the circular muscle of the guinea-pig ileum (Dietrich and Kilbinger 1995), M 4 in the guinea-pig urinary bladder (Alberts 1995), both M 1 and M 2 in the guinea-pig stomach (Ogishima et al 2000), and both M 2 and M 3 in bovine cerebral arteries (Ferrer et al 1992).…”

Section: Introductionmentioning

confidence: 97%

Heterogeneity of release-inhibiting muscarinic autoreceptors in heart atria and urinary bladder: a study with M 2 - and M 4 -receptor-deficient mice

Zhou

Meyer

Starke

et al. 2002

Naunyn-Schmiedeberg's Archives of Pharmacology

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Release-inhibiting muscarinic autoreceptors were studied in heart atria and the urinary bladder of NMRI mice, M(2)-receptor-deficient mice, M(4)-receptor-deficient mice, and wildtype mice sharing the genetic background of the knockout animals. Segments of the tissues were preincubated with (3)H-choline and then superfused and stimulated electrically. In atrial segments taken from adult mice and stimulated with 120 pulses at 1 Hz, the muscarinic receptor agonist oxotremorine-M reduced the evoked overflow of tritium. Its concentration-response curves in atria from NMRI, M(2)-wildtype, M(4)-wildtype and M(2)-knockout mice were similar, with maximal inhibition by about 75%. In atria from M(4)-knockout mice, the maximal inhibitory effect of oxotremorine-M was reduced to 57%. The concentration-response curves of oxotremorine-M were shifted to the right by ipratropium, methoctramine and pirenzepine. Methoctramine and pirenzepine were approximately equipotent antagonists in all strains except in M(4)-knockout atria in which methoctramine was more potent than pirenzepine. When atria from adult NMRI mice were stimulated by 360 pulses at 3 Hz, ipratropium increased the evoked overflow of tritium both in the absence and in the presence of physostigmine (0.1 microM). In atria taken from 1-day-old NMRI mice, oxotremorine-M failed to reduce the evoked overflow of tritium. In bladder segments taken from adult mice, superfused with medium containing oxotremorine-M (1 microM), and stimulated by 360 pulses at 3 Hz, ipratropium increased the evoked overflow of tritium. Its concentration-response curves in preparations from NMRI, M(2)-wildtype, M(4)-wildtype and M(2)-knockout mice were similar. There was one exception: ipratropium failed to cause an increase in bladder pieces from M(4)-knockout mice. Methoctramine and pirenzepine also increased the evoked overflow of tritium in all strains except the M(4)-knockout. The two antagonists were approximately equipotent in NMRI, M(4)-wildtype and M(2)-knockout preparations but methoctramine was less potent than pirenzepine in M(2)-wildtype preparations. When bladder pieces from adult NMRI mice were superfused with oxotremorine-M-free medium and stimulated by 360 pulses at 3 Hz, ipratropium increased the evoked overflow of tritium in the presence of physostigmine (0.1 microM) but not in its absence. In bladder segments taken from 1-day-old NMRI mice and superfused with medium containing oxotremorine-M (1 microM), ipratropium increased the evoked overflow of tritium in the same way as in adult tissue. It is concluded that NMRI mice and the two wildtype strains are similar in their muscarinic autoreceptors. In atria, the autoreceptors are heterogeneous. Some are M(4). The non-M(4)-autoreceptors probably are M(2). In the bladder, the autoreceptors are exclusively M(4). In both tissues, the autoreceptors are activated by previously released acetylcholine under appropriate conditions.

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Muscarine receptor types mediating autoinhibition of acetylcholine release and sphincter contraction in the guinea-pig iris

Cited by 24 publications

References 24 publications

Characterization of prejunctional muscarinic autoreceptors in the guinea‐pig trachea

Characterization of prejunctional muscarinic autoreceptors in the guinea‐pig trachea

Characterization of muscarinic receptors mediating relaxation and contraction in the rat iris dilator muscle

Heterogeneity of release-inhibiting muscarinic autoreceptors in heart atria and urinary bladder: a study with M 2 - and M 4 -receptor-deficient mice

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