Receptors involved in the positive inotropic action induced by dopamine on the ventricle of a 7‐day‐old chick embryo heart

Abstract

Earlier experiments only revealed involvement of sympathetic pre-synaptic dopaminergic receptors in dopamine induced inotropism in myocardium. We therefore used electrically stimulated (1 Hz) isolated 7-day-old chick embryo heart ventricles, thought to be devoid of functional sympathetic nerves, to re-investigate post-synaptic receptors involvement and particularly that of dopaminergic receptors in the positive inotropic effect of dopamine. The results showed that noradrenaline, isoprenaline and dopamine produced a positive inotropic effect with a similar efficacy and with an order of potency as follows: Isoprenaline = Noradrenaline > Dopamine. Tyramine induced no significant modification of the "initial tension" indicating that functional sympathetic innervation and/or releasable endogenous catecholamines were not demonstrable in the 7-day-old chick embryo heart ventricle. Propranolol (1 microM) competitively antagonized the positive inotropic response to isoprenaline, noradrenaline and dopamine, meanwhile phentolamine (3 microM) failed to significantly modify the effects of both noradrenaline and dopamine, indicating that these catecholamines induced their positive inotropic effects via stimulation of beta-adrenoceptors; involvement of alpha-adrenergic receptors stimulation was not demonstrable in these effects. Moreover, haloperidol (2 microM) antagonized the positive inotropic response to dopamine but had not any significant effect on the response to isoprenaline. The combined application of both propranolol and haloperidol antagonized the positive inotropic response to dopamine to a greater extent than when these two antagonists were given alone. Consequently, post-synaptic dopaminergic receptors were also involved in the positive inotropic effect of dopamine. Furthermore, in preparations in which sodium channels were inactivated by high potassium physiological salt solution, high concentrations of dopamine (0.1 mM to 1 mM) induced a slow developing electrical and positive inotropic responses which were also inhibited by propranolol and haloperidol, but not by phentolamine. These latter results indicated that like beta-adrenergic stimulation, the slow inward calcium current activated by stimulation of adenylate cyclase, was at least in part involved in the positive inotropic response to dopamine. In conclusion, dopamine induced its positive inotropism via stimulation of post-synaptic beta-adrenergic and dopaminergic receptors. The contribution of dopaminergic receptors in this positive inotropic effect might be of the DA-2 receptors since haloperidol used had been reported to be more DA-2 than DA-1 antagonist. These DA-2 receptors subtypes would mediate activation of adenylate cyclase.

Modulation of the Negative Inotropic Effect of Haloperidol by Drugs with Positive Inotropic Effects in Isolated Rabbit Heart

“…The highest pD) 2 value and the lowest slope and E max were reported for haloperidol combined with dopamine. Accordingly, it could be suggested that interaction of haloperidol with dopamine at dopamine D 2 receptors is implicated in the negative inotropic effect of haloperidol [38]. However, our results showed that the pattern of interference of dopamine with haloperidol was of a noncompetitive pattern.…”

“…The dopamine D 2 receptors are involved in the direct positive inotropic effect of dopamine, as dopamine increases [Ca 2+ ] i through actions mediated by dopamine D 2 receptors [37]. Moreover, it has been reported that haloperidol reduces the inotropic effect of dopamine [36,38] and of dopaminergic drugs [39]. In this study, dopamine diminished the negative inotropic effect of haloperidol.…”

2[125I]Iodomelatonin binding and interaction with β‐adrenergic signaling in chick heart/coronary artery physiology

“…Whether these early appearing receptors are functional is not known. Chick myocytes were responsive to catecholamines at E7 [34].…”

“…Whether these early appearing receptors are functional is not known. Chick myocytes were responsive to catecholamines at E7 [34]. When E15 chick embryos were challenged with the inotropic hormones isoproterenol or dopamine, [ 125 I]Mel binding densities in the heart increased, indicating that they can be regulated at E15.…”

Inotropic, Chronotropic, and Arrhythmogenic Effects of Dopamine on the Isolated Working Heart of Rabbit

“…6B). The receptors producing the direct inotropic effects of DA in the heart were reported for rabbit [30,31] and man [32] to be β-and α-adrenoceptors, for guinea pig [9] and rat [33] to be β-adrenoceptor only, and for chick embryo [34] to be β-adrenoceptor and subtype DA2-receptors. DA has been shown to increase L-type Ca 2+ currents and to produce the inotropic effect that is mediated through the direct stimulation of β-adrenoceptor in the single atrial and ventricular myocytes of the rat [33].…”