Identification and characterization of histamine H1‐ and H2‐receptors in guinea‐pig left atrial membranes by [3H]‐mepyramine and [3H]‐tiotidine binding

Hattori, Yoshiyuki; Endou, Masayuki; Gando, Satoshi; Kanno, Morio

doi:10.1111/j.1476-5381.1991.tb09829.x

Cited by 21 publications

(11 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Preincubation of CHO-gpH 1 cell membranes with this GTP␥S concentration induced a significant decrease in the affinity of mepyramine for the gp-H 1 r, shifting the homologous displacement curves of mepyramine from a pIC 50 value of 8.77 Ϯ 0.08 in the absence of GTP␥S to a pIC 50 value of 7.44 Ϯ 0.07 in the presence of GTP␥S (p Ͻ 0.01, n ϭ 5). These results are in agreement with previous observations made with the gp-H 1 r expressed in atrial membranes (22). Overexpression of G␣ 11 proteins had the opposite effect, inducing a leftward shift in the homologous displacement curves to a pIC 50 value of 9.68 Ϯ 0.08 (p Ͻ 0.01 versus non transfected cells, n ϭ 8) (Fig.…”

Section: Mepyramine Binding and Inverse Agonism At The Stably Expresssupporting

confidence: 93%

Mepyramine, a Histamine H1 Receptor Inverse Agonist, Binds Preferentially to a G Protein-coupled Form of the Receptor and Sequesters G Protein

Fitzsimons

Monczor

Fernández

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

Accurate characterization of the molecular mechanisms of the action of ligands is an extremely important issue for their appropriate research, pharmacological, and therapeutic uses. In view of this fact, the aim of the present work was to investigate the mechanisms involved in the actions of mepyramine at the guinea pig H 1 receptor stably expressed in Chinese hamster ovary cells. We found that mepyramine is able to decrease the basal constitutive activity of the guinea pig H 1 receptor, to bind with high affinity to a G q/11 protein-coupled form of the receptor and to promote a G protein-coupled inactive state of the H 1 receptor that interferes with the G q/11 -mediated signaling of the endogenously expressed ATP receptor, as predicted by the Cubic Ternary Complex Model of receptor occupancy. The effect of mepyramine on ATP-induced signaling was specifically neutralized by G␣ 11 overexpression, indicating that mepyramine is able to reduce G protein availability for other non-related receptors associated with the same signaling pathway. Finally, we found a loss of mepyramine efficacy in decreasing basal levels of intracellular calcium at high G␣ 11 expression levels, which can be theoretically explained in terms of high H 1 receptor constitutive activity. The whole of the present work sheds new light on H 1 receptor pharmacology and the mechanisms H 1 receptor inverse agonists could use to exert their observed negative efficacy.

show abstract

Section: Mepyramine Binding and Inverse Agonism At The Stably Expresssupporting

confidence: 93%

Mepyramine, a Histamine H1 Receptor Inverse Agonist, Binds Preferentially to a G Protein-coupled Form of the Receptor and Sequesters G Protein

Fitzsimons

Monczor

Fernández

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Indeed these histamine competition curves were best fitted by a two-site model. As with other G-protein-coupled receptors (Severne et al, 1986;Convents et al, 1987), histamine receptors are likely to behave as a heterogeneous population with respect to agonist binding (Hattori et al, 1991), but as a homogeneous population with respect to antagonists. The receptors with high affinity for agonist are presumed to undergo functional coupling to G proteins, whereas receptors with low affinity for agonist should be unable to couple (Birnbaumer et al, 1990).…”

Section: Discussionmentioning

confidence: 99%

Stable Expression of Human H₁‐histamine‐receptor cDNA in Chinese Hamster Ovary Cells

Moguilevsky

Varsalona

Noyer

et al. 1994

European Journal of Biochemistry

View full text Add to dashboard Cite

A cDNA clone for the histamine HI receptor was isolated from a human lung cDNA library; it encoded a protein of 487 amino acids which showed characteristic features of G-protein-coupled receptors. The percentages of identity of the deduced amino acid sequence with bovine, rat and guinea pig H, histamine receptors were 82.6%, 79.4% and 73.3%, respectively, whereas these percentages decreased to 74.6%, 66% and 56.7% for the amino acid sequence of the third intracellular loop. The human H,-receptor cDNA was transfected into Chinese hamster ovary cells (CHO) via an eukaryotic expression vector ; the receptor protein present on cell membranes specifically bound [3H]mepyramine with a Kd of 3.7 nM. The binding was displaced by H,-histamine-receptor antagonists and histamine. Northern blot analysis indicated the presence of two histamine HI receptor mRNAs of 3.5 kb and 4

show abstract

“…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.…”

mentioning

confidence: 99%

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

Self Cite

View full text Add to dashboard Cite

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...

show abstract

Identification and characterization of histamine H₁‐ and H₂‐receptors in guinea‐pig left atrial membranes by [³H]‐mepyramine and [³H]‐tiotidine binding

Cited by 21 publications

References 32 publications

Mepyramine, a Histamine H1 Receptor Inverse Agonist, Binds Preferentially to a G Protein-coupled Form of the Receptor and Sequesters G Protein

Mepyramine, a Histamine H1 Receptor Inverse Agonist, Binds Preferentially to a G Protein-coupled Form of the Receptor and Sequesters G Protein

Stable Expression of Human H₁‐histamine‐receptor cDNA in Chinese Hamster Ovary Cells

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

Contact Info

Product

Resources

About

Identification and characterization of histamine H1‐ and H2‐receptors in guinea‐pig left atrial membranes by [3H]‐mepyramine and [3H]‐tiotidine binding

Cited by 21 publications

References 32 publications

Mepyramine, a Histamine H1 Receptor Inverse Agonist, Binds Preferentially to a G Protein-coupled Form of the Receptor and Sequesters G Protein

Mepyramine, a Histamine H1 Receptor Inverse Agonist, Binds Preferentially to a G Protein-coupled Form of the Receptor and Sequesters G Protein

Stable Expression of Human H1‐histamine‐receptor cDNA in Chinese Hamster Ovary Cells

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

Contact Info

Product

Resources

About

Identification and characterization of histamine H₁‐ and H₂‐receptors in guinea‐pig left atrial membranes by [³H]‐mepyramine and [³H]‐tiotidine binding

Stable Expression of Human H₁‐histamine‐receptor cDNA in Chinese Hamster Ovary Cells

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