Antimuscarinic action of quinidine on the heart? A study in myocardial preparations from cat hearts

Nawrath, Hermann; Sack, Ulrich; Zong, Xin

doi:10.1111/j.1476-5381.1984.tb10749.x

Cited by 7 publications

(1 citation statement)

References 34 publications

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“…Adenosine exerted a concentration-dependent negative inotropic effect in cat atrial heart muscle ( (1 mmol -1') reduced the force of contraction (F.) by about 30%. Comparatively, the negative inotropic effect of acetylcholine was achieved at much lower concentrations, and full depression of Fc was observed at 1 pmol 1-1 (Nawrath et al, 1984). In the presence of dipyridamole lOpmoll P, the concentration-response curve for adenosine was not significantly affected.…”

Section: Atrial Preparationsmentioning

confidence: 87%

Pronounced cholinergic but only moderate purinergic effects in isolated atrial and ventricular heart muscle from cats

Kemmer

Jakob

Nawrath

1989

British J Pharmacology

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1 The effects of cholinergic and purinergic stimulation on action potential, force of contraction and 86Rb efflux were investigated in cat atrial and/or ventricular heart muscle. 2 Acetylcholine and carbachol exerted a concentration-dependent negative inotropic effect in cat atrial heart muscle. Carbachol lOpmoll11 completely abolished the force of contraction and increased the rate constant of 86Rb efflux 2-3 fold, whereas the action potential duration was shortened to about b of its length under control conditions. 3 The effects of acetylcholine and carbachol in cat atrial heart muscle were mimicked, qualitatively, by adenosine and its analogues 5'-(N-ethyl)-carboxamido-adenosine (NECA) and (-)-N6-4R-phenyl-isopropyl)-adenosine (R-PIA). Maximal purinergic effects, however, amounted to about 15-50% in comparison to those of cholinergic stimulation. 4 In cat ventricular heart muscle, cholinergic or purinergic stimulation had no significant effects on the force of contraction in the absence of a cyclic AMP-dependent positive inotropic effect. Carbachol antagonized the positive inotropic effect elicited by either 3-isobutyl-1-methylxanthine, isoprenaline or cyclic 8(4-chlorphenylthio)adenosine-3':5'-monophosphate; NECA and R-PIA were less effective. The inhibition by carbachol of the effects of isoprenaline was not related to a change in the rate constant of 86Rb efflux. 5 It is concluded that the effects of cholinoceptor and purinoceptor agonists in the cat heart involve a change in the potassium conductance in the atrium, whereas the effects in the ventricle may be related to changes of intracellular cyclic AMP levels. It seems reasonable to assume that, in comparison to cholinergic stimulation, a low density of purinoceptors in the cat heart is responsible for the relatively weak effects of adenosine agonists in this species.

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Section: Atrial Preparationsmentioning

confidence: 87%

Pronounced cholinergic but only moderate purinergic effects in isolated atrial and ventricular heart muscle from cats

Kemmer

Jakob

Nawrath

1989

British J Pharmacology

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Positive inotropic response to 5-HT in human atrial but not in ventricular heart muscle

Jahnel

Rupp

Ertl

et al. 1992

Naunyn-Schmiedeberg's Arch Pharmacol

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The effects of 5-hydroxytryptamine (5-HT) on force of contraction (FC), action potential (AP) and calcium current (ICa) were studied in human right atrial and left ventricular heart muscle. 5-HT exerted a concentration-dependent increase in FC in multicellular atrial preparations; the EC50 was approximately 3 x 10(-7) mol/l. Maximal increases in FC (252 +/- 58% of control values; mean +/- SEM, n = 6) were obtained at 5-HT 10(-5) mol/l. At this concentration, ICa was increased four- to sevenfold in enzymatically isolated atrial myocytes. In contrast, ventricular preparations did not respond to 5-HT; FC, AP and ICa remained unaffected. In the same preparations, FC was increased by isoprenaline three- to fourfold. These results confirm the observation that 5-HT induces a positive inotropic effect in the human atrium, possibly mediated by activation of the adenylyl cyclase - cyclic AMP system. Our study demonstrates, however, the complete lack of functional 5-HT receptors, with respect to changes in FC, in the human ventricle. Since the positive inotropic effect of 5-HT in the human heart is obviously restricted to the atrium, our findings question the concept of developing 5-HT receptor agonists for the treatment of heart failure.

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Anticholinergic action of quinidine sulfate in the rabbit atrioventricular node

Nishimura

Huan

Habuchi

et al. 1990

Naunyn-Schmiedeberg's Arch Pharmacol

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Anticholinergic action of quinidine sulfate was electrophysiologically studied by recording spontaneous action potentials and membrane current of the rabbit atrioventricular node. In the presence of 0.1 mumol/l carbachol, the spontaneous activity of the atrioventricular nodal preparations was markedly inhibited, whereas subsequent addition of 1, 5 and 20 mumol/l quinidine restored automaticity in a concentration-dependent manner. In some preparations, quinidine at concentrations of 5 mumol/l and higher slowed the spontaneous activity by its direct membrane action even in the presence of carbachol. The dose-response curve for acetylcholine action on the spontaneous firing frequency showed that one molecule of acetylcholine bound to one muscarinic receptor of the atrioventricular node cell (Hill coefficient = 1.2). A parallel shift of this curve towards higher acetylcholine concentrations was observed at 0.03, 0.1 and 0.3 mumol/l but not at 1 and 3 mumol/l quinidine, suggesting a noncompetitive antagonism of quinidine against acetylcholine. Voltage clamp experiments revealed that 5 mumol/l quinidine reduced the slow inward current, hyperpolarization-activated inward current, and delayed rectifying K+ current, through its membrane actions. Quinidine at this concentration almost completely suppressed the acetylcholine-activated K+ current, which showed a relaxation phenomenon. Hence, the direct blockage of the acetylcholine-activated K+ current by quinidine was considered responsible for the anticholinergic action of this drug. We conclude that quinidine is a non-specific ionic channel blocker that inhibits all the membrane currents in the atrioventricular node including the acetylcholine-activated K+ current.

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Antimuscarinic action of quinidine on the heart? A study in myocardial preparations from cat hearts

Cited by 7 publications

References 34 publications

Pronounced cholinergic but only moderate purinergic effects in isolated atrial and ventricular heart muscle from cats

Pronounced cholinergic but only moderate purinergic effects in isolated atrial and ventricular heart muscle from cats

Positive inotropic response to 5-HT in human atrial but not in ventricular heart muscle

Anticholinergic action of quinidine sulfate in the rabbit atrioventricular node

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