Proceedings of the International Symposium on Subtypes of Muscarinic Receptors (4th), Held in Wiesbaden (Germany, F.R.) on 20-22 July 1989

Levine, Ruth R.; Birdsall, N. J. M.; Hulme, Edward C.; Iversen, Leslie L.; Lambrecht, G.

doi:10.21236/ada224629

Cited by 2 publications

(3 citation statements)

References 6 publications

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“…Results McN-A-343 produced a relaxation of the rat duodenum and an inhibition of the twitch contraction of rabbit vas deferens with potencies comparable to those previously described (Micheletti et al, 1988;Eltze, 1988) Of the five muscarinic receptor genes (ml-m5) described (Bonner et al, 1987;1988), the first three seem to correspond to M1-M3 receptors (Levine & Birdsall, 1989). The affinity pattern of pirenzepine for these subtypes is well-known.…”

supporting

confidence: 75%

“…While receptors with low affinity for pirenzepine, originally defined as M2, have subsequently proved to be heterogeneous and have been further characterized by means of newly developed selective antagonists (Levine et al, 1988), the identification of the M1 subtype is still based on pirenzepine recognition of receptor sites occurring with high affinity. Thus, in accordance with the high sensitivity shown towards pirenzepine blockade, two recently described neuronal responses have been attributed to stimulation of M1 receptors.…”

mentioning

confidence: 99%

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4‐DAMP analogues reveal heterogeneity of M₁ muscarinic receptors

Micheletti

Giudici

Turconi

et al. 1990

British J Pharmacology

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The muscarinic receptors responsible for two effects elicited by i.e. the relaxation of the rat duodenum and the inhibition of the twitch contraction of rabbit vas deferens, were investigated by use of derivatives of 4-diphenyl acetoxy-N-methyl piperidine methobromide (4-DAMP). Both receptors had been previously identified as M1 on the basis of the high affinity shown towards pirenzepine. Schild analysis of antagonism revealed that the affinities of 4-DAMP and three of its analogues in the rat duodenum were significantly different from those estimated in rabbit vas deferens. These data indicate that distinct receptor subtypes mediate duodenal relaxation and vas deferens inhibition of twitch contraction and suggest that receptors classified as M1 by means of pirenzepine affinity constitute a heterogeneous population.introduction The classification of muscarinic receptors has long relied on the discriminative properties of the antagonist

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supporting

confidence: 75%

mentioning

confidence: 99%

4‐DAMP analogues reveal heterogeneity of M₁ muscarinic receptors

Micheletti

Giudici

Turconi

et al. 1990

British J Pharmacology

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“…As a result, we conclude that the muscarinic receptors mediating contraction in the guinea‐pig lung strip consist of a single M 2 ‐like population, with a pharmacological profile distinct from cardiac M 2 receptors. It should be added here that during a recent symposium on subtypes of muscarinic receptors (Levine & Birdsall, 1997), tripitramine was found to display affinities towards M 2 and M 2 ‐like receptors in dog tracheal and chick ileum smooth muscle and in human detrusor muscle (prejunctional autoreceptors) that ranged from 8.34 to 8.85, suggesting that tripitramine has somewhat lower affinity towards non‐cardiac M 2 ‐(like) compared to cardiac M 2 receptors.…”

Section: Discussionmentioning

confidence: 96%

Characterization of the muscarinic receptor subtype(s) mediating contraction of the guinea‐pig lung strip and inhibition of acetylcholine release in the guinea‐pig trachea with the selective muscarinic receptor antagonist tripitramine

Roffel

Davids

Elzinga

et al. 1997

British J Pharmacology

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1 The muscarinic receptor subtypes mediating contraction of the guinea-pig lung strip and inhibition of the release of acetylcholine from cholinergic vagus nerve endings in the guinea-pig trachea in vitro have previously been characterized as M 2 -like, i.e. having antagonist a nity pro®les that are qualitatively similar but quantitatively dissimilar compared to cardiac M 2 receptors. The present study sought to establish de®nitely the identity of these receptor subtypes by using the selective muscarinic receptor antagonist, tripitramine. Guinea-pig atria and guinea-pig trachea (postjunctional contractile response) were included for reference. 2 It was found that tripitramine antagonized methacholine-induced contractions of the guinea-pig lung strip with a pK B value of 8.76+0.05. Both the parallel shifts of the concentration-response curves and the slope of the Schild plot being not signi®cantly di erent from unity (when antagonist preincubation was for 2 h) indicated the involvement of a single population of receptors in the contractile response. From the pK B values obtained with tripitramine and a range of other selective muscarinic receptor antagonists (cf. Ro el et al., 1993), this single population of receptors can only be classi®ed as M 2 -like. 3 Tripitramine antagonized methacholine-induced negative chronotropic and inotropic responses in guinea-pig right and left atria with apparent pK B values of 9.4 ± 9.6. However, such values were only obtained when antagonist preincubation was relatively long and/or antagonist concentration relatively high (e.g. with 1 h at 100 or 300 nM but 3 h at 30 nM). It thus appears that low concentrations of tripitramine do not readily equilibrate with M 2 receptors in guinea-pig atria nor with M 2 -like receptors in the guinea-pig lung strip. 4 Tripitramine increased electrical ®eld stimulation-induced cholinergic twitch contractions in guineapig trachea in concentrations of 0.3 ± 100 nM, by blocking prejunctional muscarinic inhibitory autoreceptors; with higher concentrations, twitch contractions were progressively diminished, as a result of blocking postjunctional M 3 receptors (apparent pK B value 6.07+0.15). The pEC 20 value (7log concentration that increases twitch by 20% of maximum) was 8.29+0.08, which would suggest that M 4 receptors are involved in this response. 5 Oxotremorine-induced inhibition of the release of prelabelled [ 3 H]-acetylcholine from guinea-pig trachea, under conditions where there is no auto-feedback, was blocked by tripitramine (2 h preincubation) with a pK B value of 8.56+0.06. The slope of the corresponding Schild plot was not signi®cantly di erent from unity, which together with the parallel shifts of the concentration-response curves indicated the involvement of a single muscarinic receptor subtype. 6 Since the pK B value for tripitramine at prejunctional receptors in guinea-pig trachea is in between the a nities towards M 2 and M 4 receptors, correlation plots were constructed to compare the pK B values obtained with tripitramine and a ran...

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Proceedings of the International Symposium on Subtypes of Muscarinic Receptors (4th), Held in Wiesbaden (Germany, F.R.) on 20-22 July 1989

Cited by 2 publications

References 6 publications

4‐DAMP analogues reveal heterogeneity of M₁ muscarinic receptors

4‐DAMP analogues reveal heterogeneity of M₁ muscarinic receptors

Characterization of the muscarinic receptor subtype(s) mediating contraction of the guinea‐pig lung strip and inhibition of acetylcholine release in the guinea‐pig trachea with the selective muscarinic receptor antagonist tripitramine

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Proceedings of the International Symposium on Subtypes of Muscarinic Receptors (4th), Held in Wiesbaden (Germany, F.R.) on 20-22 July 1989

Cited by 2 publications

References 6 publications

4‐DAMP analogues reveal heterogeneity of M1 muscarinic receptors

4‐DAMP analogues reveal heterogeneity of M1 muscarinic receptors

Characterization of the muscarinic receptor subtype(s) mediating contraction of the guinea‐pig lung strip and inhibition of acetylcholine release in the guinea‐pig trachea with the selective muscarinic receptor antagonist tripitramine

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4‐DAMP analogues reveal heterogeneity of M₁ muscarinic receptors

4‐DAMP analogues reveal heterogeneity of M₁ muscarinic receptors