Pharmacological evidence for cardiac muscarinic receptor subtypes

Chassaing, Chantal; Dureng, G; Baissat, J.; Duchêne-Marullaz, P

doi:10.1016/0024-3205(84)90270-4

Cited by 19 publications

(12 citation statements)

References 26 publications

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“…However, our results are at variance with those of Chaissing et al (1984) in that no selectivity was seen using carbachol or arecoline. In the present study the majority of agonists studied showed no discrimination.…”

Section: Discussioncontrasting

confidence: 57%

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Action of agonists and antagonists at muscarinic receptors present on ileum and atria in vitro

Clague

Eglen

Strachan

et al. 1985

British J Pharmacology

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1 The action of 'selective' agonists and antagonists at muscarinic receptors mediating ileal contractions, and the rate and force of atrial contractions has been assessed. 2 The effect of nicotinic receptor stimulation, catecholamine release and acetylcholinesterase (AChE) action on muscarinic activity has also been assessed. 3 The nicotinic actions of carbachol did not affect its agonist potency nor the antagonist affinity data obtained when this agonist was used in atrial and ileal preparations. 4 Antagonist data indicated that muscarinic receptors mediating the rate and force of atrial contractions did not differ. Differences in agonist potencies at these two muscarinic receptors were attributable to either differences in intrinsic efficacy or susceptibility to the action of acetylcholinesterase. The small differences in agonist potency observed between atrial and ileal muscarinic receptors were considered not sufficient to indicate receptor heterogeneity. 5 The pirenzepine affinity data indicated that all three receptors are of the M2 type. Affinity data using secoverine and 4-diphenyl-acetoxy-N-methyl piperidine methiodide indicated that ileal and atrial muscarinic receptors differ. Data obtained using gallamine, pancuronium and stercuronium cannot be regarded as indicative of receptor affinity since the antagonism is not competitive; it did nonetheless corroborate the conclusion that ileal and atrial muscarinic receptors are different.

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Section: Discussioncontrasting

confidence: 57%

“…Barlow et al (1980), using data derived from agonist studies, have proposed that atrial muscarinic receptors mediating negative inotropic and chronotropic effects differ. This has been supported by Chaissing et al (1984) and Mutschler & Lambrecht (1984).…”

Section: Introductionmentioning

confidence: 99%

Action of agonists and antagonists at muscarinic receptors present on ileum and atria in vitro

Clague

Eglen

Strachan

et al. 1985

British J Pharmacology

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“…Thus, Barlow et al (1980) using 3-acetoxy N-methylpiperidine methiodide (3-AMP) have suggested that atrial muscarinic receptors mediating effects on atrial contractility differ from those mediating effects on atrial rate. A similar conclusion has been reached by Chassaing et al (1984) and Mutschler & Lambrecht (1984) employing various agonists in functional assays. Subsequent studies by Barlow & Shepherd (1985) and Barlow & Weston-Smith (1985), however, showed no convincing differences between effects on atrial rate and effects on atrial force and the original selectivity observed with 3-AMP was probably due to different cholinesterase activities in right and left atrium.…”

Section: Introductionsupporting

confidence: 63%

“…Acetylcholine and 3-AMP methiodide which are substrates of cholinesterase showed similar affinity in all 3 tissues in the presence of physostigmine. The isolated finding of acetylcholine selectivity (5 fold) for inotropic responses (Chassaing et al, 1984) which, however, could not be confirmed by Clague et al (1985) and Barlow & Weston-Smith (1985) thus finds no support in binding studies. In physiological in vitro experiments, ethoxyethyl trimethylammonium iodide (EOE) has been found to be 2 to 4 times more active on ileum than on atria (Barlow & Dawson, 1986;Barlow & Weston-Smith, 1985).…”

Section: Discussionmentioning

confidence: 91%

Subclassification of atrial and intestinal muscarinic receptors of the rat—direct binding studies with agonists and antagonists

Brünner

1989

British J Pharmacology

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1 Although extensively investigated, the extent of differences between receptors mediating negative inotropic and chronotropic responses is still unclear. In the present study atrial and intestinal muscarinic receptors were identified by [3H]-N-methyl-scopolamine ([3H]-NMS) binding and the affinities of some presumably inotropy-or chronotropy-selective agonists and several antagonists determined. 2 All the agonists tested showed similar affinity for right and left atrial receptors. Accepting an affinity difference of 0.4 log units as experimental error, none of the agonists tested was selective for either atrium. 3 Affinity differences of the cardioselective antagonists himbacine, AF-DX 116 and methoctramine and the Ml-selective antagonist dicyclomine for right and left atrial muscarinic receptors were also minimal (less than 2 fold selective). When compared to intestinal receptors, AF-DX 116 was 3 to 4 fold, methoctramine 10 to 13 fold selective and himbacine and dicyclomine non-selective. 4 These data provide evidence for differences between atrial and intestinal but not between right and left atrial muscarinic receptors.

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“…APE has been shown to have cardiovascular effects. APE produces negative chronotropic and inotropic effects in isolated atria [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Activation of muscarinic K+ channels by arecaidine propargyl ester in isolated guinea-pig atrial myocytes

Chen

2005

J Biomed Sci

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Arecaidine propargyl ester (APE) was developed as a potential candidate compound for the treatment of Alzheimer's disease. APE has been shown to have cardiovascular effects. APE produces negative chronotropic and inotropic effects in isolated atria. However, the ionic mechanisms underlying the cardiovascular effects of APE in guinea-pig atria are unclear. The aims of this study were: (1) to examine the shortening effect of APE on action potential duration (APD) and to compare the difference in potency between APE and muscarine in isolated single guinea-pig atrial myocytes by using the current clamp method, (2) to examine by using patch clamp techniques the ionic mechanisms underlying the cardiac effects of APE, and (3) to determine whether the cardiac effects caused by APE affect the usefulness of APE as a potential candidate for the treatment of Alzheimer's disease. The APE significantly reduced the APD in guinea-pig atria and produced no direct effect on ventricular myocytes. APE is approximately 20 times as potent as muscarine in shortening the APD. Attenuation of the APD was consistently accompanied by a hyperpolarization of the resting membrane potential in a concentration-dependent manner. The APE activated muscarinic K+ channels and increased potassium conductance in guinea-pig atrial myocytes. In the cell-attached configuration, the APE contained in the pipette increased the channel-opening probability and decreased the closed-state time interval. The proposal that APE can be used as a potential remedy for the treatment of Alzheimer's disease should be taken into consideration the undesirable cardiovascular side effects that APE causes at lower concentrations.

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Pharmacological evidence for cardiac muscarinic receptor subtypes

Cited by 19 publications

References 26 publications

Action of agonists and antagonists at muscarinic receptors present on ileum and atria in vitro

Action of agonists and antagonists at muscarinic receptors present on ileum and atria in vitro

Subclassification of atrial and intestinal muscarinic receptors of the rat—direct binding studies with agonists and antagonists

Activation of muscarinic K+ channels by arecaidine propargyl ester in isolated guinea-pig atrial myocytes

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