Prejunctional muscarine receptors in the rabbit ear artery differ from M1, M2 and M3 muscarine receptors

Darroch, S.; Choo, L. K.; Mitchelson, F.

doi:10.1007/bf00168689

Cited by 13 publications

(2 citation statements)

References 39 publications

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“…trihexyphenidyl (anity pro®le as compiled from Lazareno et al, 1990;DoÈ rje et al, 1991;Waelbroeck et al, 1992;Bognar et al, 1992;Doods et al, 1993;Onali et al, 1994 being M 1 (9.0) = M 4 (8.8) 4 M 3 (8.3) 4 M 2 (7.8)) and tropicamide (M 4 (7.8) 4 M 1 (7.3) = M 2 (7.2) = M 3 (7.2); Lararenzo et al, 1990;Doods et al, 1993;Lazareno & Birdsall, 1993;Rinken, 1995). It was found that trihexyphenidyl behaved like the M 3 selective compounds, yielding a pK B value (7.64+0.10, n=12, estimated with concentrations ranging from 0.03 ± 1.0 mM, slope of the Schild plot 1.15+0.09, n=3) that resembled M 2 but not M 3 or M 4 anities; by contrast, tropicamide yielded a pK B value (6.57+0.06, n=14, 0.3 ± 30 mM, slope 1.03+0.03) that was actually too low to correlate to any known muscarinic receptor subtype, behaviour which is reminiscent of trihexyphenidyl in rabbit iris sphincter and rabbit ear artery (Bognar et al, 1992;Darroch et al, 1992). Clearly, these compounds do not support a characterization of the muscarinic receptors mediating contraction of the guinea-pig lung strip as M 4 .…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

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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“…In the rabbit ear artery the sympathetic nerves appear to have at least two types of inhibitory prejunctional muscarine receptors as a number of antagonists indicate different affinities for CCh and McN (Choo et al 1985(Choo et al , 1986Darroch et al 1990). For example pirenzepine was found to be approximately 20-fold more potent and AF-DX 116 three-fold less potent when McN rather than CCh was the agonist.…”

Section: Discussionmentioning

confidence: 99%

SELECTIVE INHIBITION OF RESPONSES TO CARBACHOL AND McN‐A‐343 IN THE RABBIT VAS DEFERENS

Choo¹,

Mitchelson²

1990

Clin Exp Pharma Physio

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1. The effect of several selective muscarine receptor antagonists were evaluated on the responses of carbachol (CCh) and McN-A-343 (McN) during sympathetic nerve stimulation in the rabbit vas deferens. 2. The muscarine M1 receptor antagonist pirenzepine exhibited similar apparent pKB values for antagonism of the prejunctional inhibitory response of either CCh (pKB, 8.2) or McN (pKB, 8.5) on sympathetic nerve stimulation. 3. The muscarine M2 receptor antagonists, pancuronium and the bisalkyl ammonium compound 'C7/3-phth' were selective inhibitors of the postjunctional facilitatory response produced by CCh on sympathetic nerve stimulation. They were also 17- and three-fold, respectively, less potent against the inhibitory responses of McN on sympathetic nerve stimulation. The apparent pKB value of pancuronium on the inhibitory response produced by CCh did not differ significantly (P greater than 0.05) from that using McN. A similar finding was made for C7/3-phth. 4. Selective blockade of the inhibitory response to CCh with pirenzepine (0.03 or 0.5 mumol/L) did not significantly (P greater than 0.05) modify the apparent pKB value for pancuronium on the facilitatory response of CCh. 5. Selective blockade of the facilitatory response to CCh with a low concentration of pancuronium (0.5 mumol/L) did not significantly (P greater than 0.05) modify the apparent pKB value for pancuronium (30 mumol/L) on the inhibitory response of CCh. 6. It is suggested that CCh and McN activate the same prejunctional M1 muscarine receptor and that pancuronium is the most selective of the muscarine M2 receptor antagonists presently tested in this preparation for distinguishing between muscarine M1 and M2 receptors.

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Airways Smooth Muscle: Neurotransmitters, Amines, Lipid Mediators and Signal Transduction

Raeburn¹,

Giembycz²

1995

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Prejunctional muscarine receptors in the rabbit ear artery differ from M1, M2 and M3 muscarine receptors

Cited by 13 publications

References 39 publications

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

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

SELECTIVE INHIBITION OF RESPONSES TO CARBACHOL AND McN‐A‐343 IN THE RABBIT VAS DEFERENS

Airways Smooth Muscle: Neurotransmitters, Amines, Lipid Mediators and Signal Transduction

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