Histamine Receptors Mediating a Positive Inotropic Effect in Guinea Pig and Rabbit Ventricular Myocardium: Distribution of the Receptors and Their Possible Intracellular Coupling Processes

Hattori, Yoshiyuki; Gando, Satoshi; Nagashima, Masato; Kanno, Morio

doi:10.1254/jjp.65.327

Cited by 14 publications

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“…Although the positive inotropic effect of histamine in the left atrium of the rabbit is exclusively mediated by H 2 receptors (Hattori et al, 1988), in the guinea pig, the positive inotropic effect in the left atrium is mediated entirely by H 1 receptors (Steinberg and Holland, 1975;Verma and McNeill, 1977). On the other hand, in guinea pig ventricular muscle, the positive inotropic effect of histamine is mediated predominantly by H 2 receptors (Hattori et al, 1994), whereas H 1 receptors almost exclusively mediate the inotropic effect in the rabbit ventricle (Hattori et al, 1990(Hattori et al, , 1994. Thus, the particular distribution of H 1 and H 2 receptors in guinea pig and rabbit myocardial tissues that we report here, well explains previous pharmacological findings.…”

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confidence: 87%

“…Moreover, different receptor subtypes mediate the inotropic effect in different parts of the heart within the same species. In the guinea pig heart, only H 1 receptors are responsible for the positive inotropic effect of histamine in left atrium, whereas H 2 receptors predominantly mediate its positive inotropic effect in ventricle (Steinberg and Holland, 1975;Verma and McNeill, 1977;Hattori et al, 1994). In contrast, in the rabbit heart, H 2 receptors mediate the posi-tive inotropic effect of histamine in left atrium, whereas H 1 receptors are predominantly involved in the ventricle (Hattori et al, 1988(Hattori et al, , 1990(Hattori et al, , 1994.…”

mentioning

confidence: 99%

“…In the guinea pig heart, only H 1 receptors are responsible for the positive inotropic effect of histamine in left atrium, whereas H 2 receptors predominantly mediate its positive inotropic effect in ventricle (Steinberg and Holland, 1975;Verma and McNeill, 1977;Hattori et al, 1994). In contrast, in the rabbit heart, H 2 receptors mediate the posi-tive inotropic effect of histamine in left atrium, whereas H 1 receptors are predominantly involved in the ventricle (Hattori et al, 1988(Hattori et al, , 1990(Hattori et al, , 1994. On the other hand, the positive inotropic effect of histamine in the human heart, whether in the atria or in the ventricle, is invariably blocked by cimetidine, and not by pyrilamine, indicating an exclusive H 2 receptor involvement (Eckel et al, 1982;Du et al, 1993).…”

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confidence: 99%

“…Yet, these studies have been hampered by high nonspecific binding and/or significant binding to secondary nonhistamine-receptor sites (Chang et al, 1979;Hill and Young, 1980;Foreman et al, 1985;Rising and Norris, 1985;Liu et al, 1992). Thus, many of the radioligands used to label H 1 and H 2 receptors seem to be of limited value for an accurate estimate of the distribution and molecular characteristics of cardiac histamine receptors (Hattori et al, 1991(Hattori et al, , 1994.…”

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Histamine H₁and H₂Receptor Gene and Protein Levels Are Differentially Expressed in the Hearts of Rodents and Humans

Matsuda¹,

Jesmin²,

Takahashi³

et al. 2004

J Pharmacol Exp Ther

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Histamine is highly concentrated in the heart of animals and humans. Excessive release in pathophysiological conditions, such as immediate hypersensitivity and septic shock, causes cardiac dysfunction and arrhythmias. Previous pharmacological studies revealed that H 1 and H 2 receptors mediate these effects. Yet, an accurate estimate of the distribution and molecular characteristics of cardiac histamine receptors is missing. Recently, the genes encoding H 1 and H 2 receptors have been cloned, and the amino acid sequence and protein structure have been elucidated. Accordingly, we analyzed gene and protein expression levels of H 1 and H 2 receptors in atria and ventricles of guinea pig, rabbit, rat, and human hearts. With immunocytochemical techniques, we examined the regional expression of H 1 and H 2 receptor proteins in the sinoatrial and atrioventricular nodes and surrounding myocardium of the guinea pig heart. Northern and Western blot studies revealed that cardiac histamine H 1 and H 2 receptors are variably distributed among different mammalian species and different regions of the heart, whereas H 2 receptors are abundantly expressed in human atrial and ventricular myocardium. These findings agree with those of previous pharmacological studies, clearly demonstrating that the responses of the heart to histamine depend on the expression level of H 1 and H 2 receptors. The highly abundant expression of H 2 receptors in the human heart substantiates histamine arrhythmogenicity in various disease states. The new knowledge of a differential distribution of histamine receptor subtypes in the human heart will foster a better understanding of histamine roles in cardiovascular pathophysiology and may contribute to new therapeutic approaches to histamine-induced cardiac dysfunctions.The actions of histamine as a cardiac stimulant have been appreciated for more than 90 years since the seminal work of Dale and Laidlaw (1910). The primary and direct actions of histamine in the heart are characterized by an increase in sinus rate and ventricular automaticity, a decrease in AV conduction velocity, and an increase in force of contraction (Levi et al., 1991;Hattori, 1999). Because histamine is present in high concentrations in cardiac tissues in most animal species, including humans (Bristow et al., 1982;Wolff and Levi, 1986), its release from cardiac stores and its subsequent actions on the heart may be of importance in pathological conditions associated with histamine release (Levi, 1988). In this context, we recently reported that superinduction of histamine receptor gene products and histamine overproduction contribute to the hemodynamic derangement characteristic of septic shock (Matsuda et al., 2002).The negative dromotropic and positive chronotropic effects of histamine invariably result from the activation of H 1 and H 2 receptors, respectively (Levi et al., 1991;Hattori, 1999). In contrast, there is a marked species difference in the subtype of histamine receptors mediating the positive inotropic effect. Mor...

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confidence: 87%

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confidence: 99%

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confidence: 99%

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Histamine H₁and H₂Receptor Gene and Protein Levels Are Differentially Expressed in the Hearts of Rodents and Humans

Matsuda¹,

Jesmin²,

Takahashi³

et al. 2004

J Pharmacol Exp Ther

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“…In guinea pig left atria (Reinhardt et al 1974) and in rabbit papillary muscle (Elizalde et al 1986) stimulation of H 1 receptors leads to a positive inotropic effect. Molecular characterisation revealed the presence of histamine H 1 receptors in guinea pig right atria (Bennardini et al 1984), left atria (Hattori et al 1991), and in both ventricles (Chang et al 1979;Bennardini et al 1984;Kržan et al 1993, Kržan 1996Hattori et al 1994). From the photoaffinity labelling studies on guinea pig cardiac H 1 receptors, there are indications that cardiac H 1 -receptors may have different properties in comparison with H 1 receptors present in other tissues (Ruat et al 1990).…”

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confidence: 99%

Pharmacological properties of cardiovascular histamine H1 receptor binding sites: characterisation with 2-phenylhistamines

Carman-Krzan

Kržan

Schunack

1997

Naunyn-Schmiedeberg's Arch Pharmacol

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We determined and compared the molecular properties of histamine H1 receptor binding sites in bovine thoracic aorta smooth muscle and guinea pig myocardial membranes from ventricles with saturation and inhibition binding assay, using 3H-mepyramine to label the receptor and specific and selective H1 receptor agonists of the 2-phenylhistamine group as displacers of specific 3H-mepyramine binding. 3H-mepyramine binds in a saturable manner to a homogenous population of binding sites with a K(D) of 5.6 nM and a Bmax of 57 fmol/mg of protein in bovine aorta vascular smooth muscle membranes, whereas in the guinea pig myocardium high and low affinity 3H-mepyramine binding sites exist having the following molecular characteristics: a K(D) of 1.6 nM and a Bmax of 99 fmol/mg of protein (high affinity site) and a K(D) 15.0 nM and a Bmax of 466 fmol/mg of protein (low affinity site). Halogenated 2-phenylhistamines: 2-(3-fluoro-) (2-FPH), 2-(3-trifluoromethyl-) (2-triFMPH), 2-(3-chloro-) (2-CPH), 2-(3-bromo-) (2-BPH) and 2-(3-iodophenyl)histamine (2-IPH), which showed high selectivity and potency for H1 receptors in the functional pharmacological studies, were potent inhibitors of specific radioligand binding in comparison with histamine and parent nonhalogenated 2-phenylhistamine (2-PH). Their rank order of potencies and affinities differ significantly for the vascular and cardiac H1 receptor binding sites: Specific 3H-mepyramine binding to H1 receptors in bovine vascular smooth muscle membranes was displaced in a biphasic manner by 2-(3-fluoro-), 2-(3-trifluoromethyl-), 2-(3-chloro-), 2-(3-bromo-), 2-(3-iodophenyl)histamine and histamine. In guinea pig ventricular myocardium the rank order was 2-(3-iodo-), 2-(3-bromo-), histamine, 2-(3-chloro-), and 2-(3-fluorophenyl)histamine showing better correlation with the lipophilicity of the derivatives than in vascular tissue (order of lipophilicity: 2-triFMPH >2-IPH >2-BPH >2-CPH >2-FPH >>2-PH). Displacement of the radioligand binding to myocardial H1 receptor by the above drugs is (except for 2-(3-fluorophenyl)histamine), better fitted to a two-site model. 2-phenylhistamine, which acted as a moderate agonist in functional studies, displaced the radioligand in a monophasic manner and was the weakest displacer of specific radioligand binding in both model systems (pKi = 5.76--vascular and 5.57--cardiac tissue). The agonistic nature of the halogenated 2-phenylhistamine derivatives was confirmed on the molecular level, since their interaction with the H1 receptor is regulated by guanine nucleotides. GTP (0.1 mM) significantly lowered the affinities of all tested halogenated 2-phenylhistamines and histamine for H1 receptor binding site converting biphasic displacement curves, to monophasic ones, whereas GTP had no effect on the affinity of 2-PH. The results of this study support the conclusions that bovine vascular and guinea pig myocardial histamine H1 receptors differ in their molecular properties. Selective and potent H1 receptor agonists of 2-phenylhistamine class can discriminate ...

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Regulation of the Cardiovascular System by Histamine

Hattori

Matsuda

2016

Handbook of Experimental Pharmacology

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Histamine mediates a wide range of cellular responses, including allergic and inflammatory reactions, gastric acid secretion, and neurotransmission in the central nervous system. Histamine also exerts a series of actions upon the cardiovascular system but may not normally play a significant role in regulating cardiovascular function. During tissue injury, inflammation, and allergic responses, mast cells (or non-mast cells) within the tissues can release large amounts of histamine that leads to noticeable cardiovascular effects. Owing to intensive research during several decades, the distribution, function, and pathophysiological role of cardiovascular H- and H-receptors has become recognized adequately. Besides the recognized H- and H-receptor-mediated cardiovascular responses, novel roles of H- and H-receptors in cardiovascular physiology and pathophysiology have been identified over the last decade. In this review, we describe recent advances in our understanding of cardiovascular function and dysfunction mediated by histamine receptors, including H- and H-receptors, their potential mechanisms of action, and their pathological significance.

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Histamine Receptors Mediating a Positive Inotropic Effect in Guinea Pig and Rabbit Ventricular Myocardium: Distribution of the Receptors and Their Possible Intracellular Coupling Processes

Cited by 14 publications

References 25 publications

Histamine H₁and H₂Receptor Gene and Protein Levels Are Differentially Expressed in the Hearts of Rodents and Humans

Histamine H₁and H₂Receptor Gene and Protein Levels Are Differentially Expressed in the Hearts of Rodents and Humans

Pharmacological properties of cardiovascular histamine H1 receptor binding sites: characterisation with 2-phenylhistamines

Regulation of the Cardiovascular System by Histamine

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Histamine Receptors Mediating a Positive Inotropic Effect in Guinea Pig and Rabbit Ventricular Myocardium: Distribution of the Receptors and Their Possible Intracellular Coupling Processes

Cited by 14 publications

References 25 publications

Histamine H1and H2Receptor Gene and Protein Levels Are Differentially Expressed in the Hearts of Rodents and Humans

Histamine H1and H2Receptor Gene and Protein Levels Are Differentially Expressed in the Hearts of Rodents and Humans

Pharmacological properties of cardiovascular histamine H1 receptor binding sites: characterisation with 2-phenylhistamines

Regulation of the Cardiovascular System by Histamine

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Product

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Histamine H₁and H₂Receptor Gene and Protein Levels Are Differentially Expressed in the Hearts of Rodents and Humans

Histamine H₁and H₂Receptor Gene and Protein Levels Are Differentially Expressed in the Hearts of Rodents and Humans