Stimulation of histamine H-receptors produces a positive inotropic effect in the human atrium.

There is a controversy whether histamine H-receptor activation raises or lowers or does not affect contractility in the human heart. Therefore, we studied stimulation of H-receptors in isolated electrically stimulated (one beat per second) human atrial preparations (HAP). For comparison, we measured force of contraction in left atrial preparations (LA) from mice with overexpression of the histamine H-receptor in the heart (H-TG).

Clozapine is a functional antagonist at cardiac human H-histamine receptors.

Clozapine is an atypical antipsychotic (neuroleptic) drug. Clozapine binds to H-histamine receptors in vitro. We wanted to test the hypothesis that clozapine might be a functional antagonist at human cardiac H-histamine receptors.

Opposite Contractile Effects of Amphetamine-Related Hallucinogenic Drugs in the Isolated Human Atrium.

The present study examined three hallucinogenic amphetamine derivatives, namely, 2,5-dimethoxy-4-iodoamphetamine (DOI) as well as 2,5-dimethoxy-4-methylamphetamine (DOM) and 4-methylmethcathinone (mephedrone). The objective of this study was to test the hypothesis that DOI, DOM, and mephedrone would increase the contractile force in isolated human atrial preparations in a manner similar to amphetamine. To this end, we measured contractile force under isometric conditions in electrically stimulated (1 Hz) human atrial preparations obtained during open surgery.

Effects of psilocin and psilocybin on human 5-HT serotonin receptors in atrial preparations of transgenic mice and humans.

Several fungi belonging to the genus Psilocybe, also called "magic mushrooms", contain the hallucinogenic drugs psilocybin and psilocin. They are chemically related to serotonin (5-HT). In addition to being abused as drugs, they are now also being discussed or used as a treatment option for depression.

Initial Characterization of a Transgenic Mouse with Overexpression of the Human H-Histamine Receptor on the Heart.

There is a debate on whether H-histamine receptors can alter contractility in the mammalian heart. We studied here a new transgenic mouse model where we increased genetically the cardiac level of the H-histamine receptor. We wanted to know if histamine could augment or decrease contractile parameters in mice with cardiac-specific overexpression of human H-histamine receptors (H-TG) and compared these findings with those in littermate wild-type mice (WT).

Mosapride stimulates human 5-HT-serotonin receptors in the heart.

Mosapride (4-amino-5-chloro-2-ethoxy-N-[[4-[(4-fluorophenyl) methyl]-2-morpholinyl]-methyl] benzamide) is a potent agonist at gastrointestinal 5-HT receptors. Mosapride is an approved drug to treat several gastric diseases. We tested the hypothesis that mosapride also stimulates 5-HT receptors in the heart.

Effects of hallucinogenic drugs on the human heart.

Hallucinogenic drugs are used because they have effects on the central nervous system. Their hallucinogenic effects probably occur via stimulation of serotonin receptors, namely, 5-HT-serotonin receptors in the brain. However, a close study reveals that they also act on the heart, possibly increasing the force of contraction and beating rate and may lead to arrhythmias.

Effects of congeners of amphetamine on the human heart.

Central stimulatory and hallucinogenic drugs of abuse like amphetamine and most congeners of amphetamine can have cardiac harmful effects. These cardiac side effects can lead to morbidities and death. In this paper, we review current knowledge on the direct and indirect effects of these amphetamine congeners on the mammalian heart-more specifically, the isolated human heart muscle preparation.

Further investigations on the influence of protein phosphatases on the signaling of muscarinic receptors in the atria of mouse hearts.

The vagal regulation of cardiac function involves acetylcholine (ACh) receptor activation followed by negative chronotropic and negative as well as positive inotropic effects. The resulting signaling pathways may include G protein-coupled reduction in adenylyl cyclase (AC) activity, direct G protein-coupled activation of ACh-activated potassium current (I), inhibition of L-type calcium ion channels, and/or the activation of protein phosphatases. Here, we studied the role of the protein phosphatases 1 (PP1) and 2A (PP2A) for muscarinic receptor signaling in isolated atrial preparations of transgenic mice with cardiomyocyte-specific overexpression of either the catalytic subunit of PP2A (PP2A-TG) or the inhibitor-2 (I2) of PP1 (I2-TG) or in double transgenic mice overexpressing both PP2A and I2 (DT).

Contractile Effects of Amphetamine, Pseudoephedrine, Nor-pseudoephedrine (Cathine), and Cathinone on Atrial Preparations of Mice and Humans.

Amphetamine derivatives are used worldwide legally or illegally and intoxications may be accompanied by cardiac arrhythmias. Here, we tested contractile effects of cumulative applied (±)-amphetamine, pseudoephedrine, nor-pseudoephedrine (cathine), and cathinone in electrically stimulated (1 Hz) human right atrial preparations (HAP) and mouse left atrial preparations and in spontaneously beating mouse right atrial preparations. In mouse atrial preparations, amphetamine increased force of contraction and beating rate in a concentration- and time-dependent manner, starting at 1 µM in left atrial preparations to 157.

Initial characterization of a transgenic mouse with overexpression of the human D-dopamine receptor in the heart.

Dopamine can exert effects in the mammalian heart via five different dopamine receptors. There is controversy whether dopamine receptors increase contractility in the human heart. Therefore, we have generated mice that overexpress the human D-dopamine receptor in the heart (D-TG) and hypothesized that dopamine increases force of contraction and beating rate compared to wild-type mice (WT).

Cantharidin and sodium fluoride attenuate the negative inotropic effects of carbachol in the isolated human atrium.

Carbachol, an agonist at muscarinic receptors, exerts a negative inotropic effect in human atrium. Carbachol can activate protein phosphatases (PP1 or PP2A). We hypothesized that cantharidin or sodium fluoride, inhibitors of PP1 and PP2A, may attenuate a negative inotropic effect of carbachol.

Glucagon and Its Receptors in the Mammalian Heart.

Glucagon exerts effects on the mammalian heart. These effects include alterations in the force of contraction, beating rate, and changes in the cardiac conduction system axis. The cardiac effects of glucagon vary according to species, region, age, and concomitant disease.

Clonidine stimulates force of contraction via histamine H receptors in the human atrium.

Clonidine has various clinical effects mediated by agonism of α- or α-adrenoceptors and the blocking of hyperpolarization-activated-nucleotide-gated pacemaker channels (HCN). It is unknown whether clonidine can also stimulate human cardiac histamine H receptors (hHRs). We used isolated electrically stimulated left and spontaneously beating right atrial preparations from mice overexpressing the hHR specifically in the heart (H-TG), and spontaneously beating right atrial preparations of guinea pigs for comparison.

Lysergic acid diethylamide stimulates cardiac human H histamine and cardiac human 5-HT-serotonin receptors.

Lysergic acid diethylamide (LSD) is an artificial hallucinogenic drug. Thus, we hypothesized that LSD might act 5-HT serotonin receptors and/or H histamine receptors. We studied isolated electrically stimulated left atrial preparations, spontaneously beating right atrial preparations, and spontaneously beating Langendorff-perfused hearts from transgenic mice with cardiomyocyte-specific overexpression of the human 5-HT receptor (5-HT-TG) or of the H-histamine receptor (H-TG).

Methamphetamine increases force of contraction in isolated human atrial preparations through the release of noradrenaline.

We measured the cardiac contractile effects of the sympathomimetic amphetamine-like drug methamphetamine alone and in the presence of cocaine or propranolol in human atrial preparations. For a more comprehensive analysis, we also examined the effects of methamphetamine in preparations from the left and right atria of mice and, for comparison, analyzed the cardiac effects of amphetamine itself. In human atrial preparations, methamphetamine and amphetamine increased the contractile force, the relaxation rate, and the rate of tension development, and shortened the time to maximum tension and the time to relaxation.

OR-1896 increases force of contraction in the isolated human atrium.

OR-1896 ((R)-N-(4-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenyl)acetamide) is the main active metabolite of levosimendan. However, nobody has reported a positive inotropic effect of OR-1896 in isolated human cardiac preparations. The mechanism of action of OR-1896 remains controversial.

Ergometrine stimulates histamine H receptors in the isolated human atrium.

Ergometrine (6aR,9R)-N-((S)-1-hydroxypropan-2-yl)-7-methyl-4,6,6a,7,8,9-hexa-hydro-indolo-[4,3-fg]chinolin-9-carboxamide or lysergide acid β-ethanolamide or ergonovine) activates several types of serotonin and histamine receptors in the animal heart. We thus examined whether ergometrine can activate human serotonin 5-HT receptors (h5-HTR) and/or human histamine H receptors (hHR) in the heart of transgenic mice and/or in the human isolated atrium. Force of contraction or beating rates were studied in electrically stimulated left atrial or spontaneously beating right atrial preparations or spontaneously beating isolated retrogradely perfused hearts (Langendorff setup) of mice with cardiac specific overexpression of the h5-HTR (5-HT-TG) or of mice with cardiac specific overexpression of the hHR (H-TG) or in electrically stimulated human right atrial preparations obtained during cardiac surgery.

Function and Role of Histamine H Receptor in the Mammalian Heart.

Histamine can change the force of cardiac contraction and alter the beating rate in mammals, including humans. However, striking species and regional differences have been observed. Depending on the species and the cardiac region (atrium versus ventricle) studied, the contractile, chronotropic, dromotropic, and bathmotropic effects of histamine vary.

Temperature alters the inotropic, chronotropic and proarrhythmic effects of histamine in atrial muscle preparations from humans and H-receptor overexpressing mice.

We investigated whether hypothermia and hyperthermia can alter the efficacy and potency of histamine at increasing the force of cardiac contractions in mice that overexpress the human H receptor only in their cardiac myocytes (labelled H-TG). Contractile studies were performed in an organ bath on isolated, electrically driven (1 Hz) left atrial preparations and spontaneously beating right atrial preparations from H-TG mice and wild-type (WT) littermate control mice. The basal beating rate in the right atrial preparations from H-TG mice was lowered by hypothermia (23 °C) and elevated by hyperthermia (42 °C).

Role of Dopamine in the Heart in Health and Disease.

Dopamine has effects on the mammalian heart. These effects can include an increase in the force of contraction, and an elevation of the beating rate and the constriction of coronary arteries. Depending on the species studied, positive inotropic effects were strong, very modest, or absent, or even negative inotropic effects occurred.