Negative regulation of the platelet Na<sup>+</sup>/H<sup>+</sup> exchanger by trimeric G‐proteins

Willigen, Gijsbert van; Nieuwland, Rienk; Nürnberg, Bernd; Gorter, Gertie; Akkerman, Jan-Willem Ν.

doi:10.1046/j.1432-1327.2000.01813.x

Cited by 9 publications

(4 citation statements)

References 51 publications

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“…A rise in intracellular Na 1 may reverse the Na 1 /Cl --dependent noradrenaline transporter and induce carrier-mediated neurotransmitter release. H 3 R activation reduces NHE activity in sympathetic nerve terminals, leading to inhibition of noradrenaline release in myocardial ischemia (Silver et al, 2001); the mechanism is not fully understood, although a direct Ga i/o subunit/NHE interaction appears likely (van Willigen et al, 2000).…”

Section: Signaling Pathwaysmentioning

confidence: 99%

The Histamine H₃Receptor: Structure, Pharmacology, and Function

et al. 2016

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Among the four G protein-coupled receptors (H-H) identified as mediators of the biologic effects of histamine, the H receptor (HR) is distinguished for its almost exclusive expression in the nervous system and the large variety of isoforms generated by alternative splicing of the corresponding mRNA. Additionally, it exhibits dual functionality as autoreceptor and heteroreceptor, and this enables HRs to modulate the histaminergic and other neurotransmitter systems. The cloning of the HR cDNA in 1999 by Lovenberg et al. allowed for detailed studies of its molecular aspects. In this work, we review the characteristics of the HR, namely, its structure, constitutive activity, isoforms, signal transduction pathways, regional differences in expression and localization, selective agonists, antagonists and inverse agonists, dimerization with other neurotransmitter receptors, and the main presynaptic and postsynaptic effects resulting from its activation. The HR has attracted interest as a potential drug target for the treatment of several important neurologic and psychiatric disorders, such as Alzheimer and Parkinson diseases, Gilles de la Tourette syndrome, and addiction.

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Section: Signaling Pathwaysmentioning

confidence: 99%

The Histamine H₃Receptor: Structure, Pharmacology, and Function

et al. 2016

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“…The intracellular acidosis during myocardial ischemia may activate the sarcolemmal NHE-1 with subsequent Na ϩ influx, cytosolic Ca 2ϩ overflow, and ischemic contracture. Because NHE-1 is negatively regulated by inhibitory G proteins (G i␣ ), 35 it is possible that it may also contribute to the inhibition of ischemic contracture by EP 3 overexpression. In addition, Zacharowski and coworkers 36 reported that the inhibition of mitochondrial K ATP channels by 5-hydroxydecanoic acid counteracts the cardioprotection by EP 3 receptor agonists, but the role of K ATP for prostaglandinmediated cardioprotection is still unclear.…”

Section: Discussionmentioning

confidence: 99%

Cardiospecific Overexpression of the Prostaglandin EP ₃ Receptor Attenuates Ischemia-Induced Myocardial Injury

et al. 2005

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Background-The generation of prostaglandin E 2 (PGE 2 ) is significantly increased in acute myocardial ischemia and reperfusion. PGE 2 , in addition to other prostaglandins, protects the reperfused ischemic myocardium. It has been hypothesized that this cardioprotection is mediated by E-type prostaglandin receptors of the G i -coupled EP 3 subtype. Methods and Results-We tested this hypothesis by generating transgenic (tg) mice with cardiospecific overexpression of the EP 3 receptor. According to ligand binding, a 40-fold overexpression of the EP 3 receptor was achieved in membranes prepared from tg hearts compared with wild-type (wt) littermates. In isolated cardiomyocytes from tg mice, the forskolin-induced rise in cAMP was markedly attenuated, indicating coupling of the overexpressed EP 3 receptor to inhibitory G proteins (G i ) with constitutive receptor activity. There was no evidence for EP 3 receptor coupling to G q -mediated protein kinase C signaling. Isolated hearts from tg and wt mice were subjected to 60 minutes of no-flow ischemia and 45 minutes of reperfusion. In tg hearts, ischemic contracture was markedly delayed compared with wt hearts, and the ischemia-induced increase in left ventricular end-diastolic pressure was reduced by 55%. Creatine kinase and lactate dehydrogenase release was significantly decreased by 85% and 73%, respectively, compared with wt hearts. Conclusions-Constitutive prostaglandin EP 3 receptor signaling exerts a protective effect on cardiomyocytes, which is probably G i mediated and results in a remarkable attenuation of myocardial injury during ischemia and reperfusion.

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“…Second, H3R activation can reduce neurotransmitter release by inhibiting N- and P/Q-type voltage-gated calcium channels again through the Gβγ subunit ( 68 , 69 ). Third, H3R activation has been shown to reduce the activity of the sodium–proton exchanger (NHE), which is under the control of Gαi ( 70 , 71 ). Therefore, activation of H3R has opposite effects on neuronal activity to that of H1R or H2R activation.…”

Section: Histamine Receptor Signalingmentioning

confidence: 99%

Histaminergic regulation of food intake

Khouma,

Moeini,

Plamondon

et al. 2023

Front. Endocrinol.

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Histamine is a biogenic amine that acts as a neuromodulator within the brain. In the hypothalamus, histaminergic signaling contributes to the regulation of numerous physiological and homeostatic processes, including the regulation of energy balance. Histaminergic neurons project extensively throughout the hypothalamus and two histamine receptors (H1R, H3R) are strongly expressed in key hypothalamic nuclei known to regulate energy homeostasis, including the paraventricular (PVH), ventromedial (VMH), dorsomedial (DMH), and arcuate (ARC) nuclei. The activation of different histamine receptors is associated with differential effects on neuronal activity, mediated by their different G protein-coupling. Consequently, activation of H1R has opposing effects on food intake to that of H3R: H1R activation suppresses food intake, while H3R activation mediates an orexigenic response. The central histaminergic system has been implicated in atypical antipsychotic-induced weight gain and has been proposed as a potential therapeutic target for the treatment of obesity. It has also been demonstrated to interact with other major regulators of energy homeostasis, including the central melanocortin system and the adipose-derived hormone leptin. However, the exact mechanisms by which the histaminergic system contributes to the modification of these satiety signals remain underexplored. The present review focuses on recent advances in our understanding of the central histaminergic system’s role in regulating feeding and highlights unanswered questions remaining in our knowledge of the functionality of this system.

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Negative regulation of the platelet Na⁺/H⁺ exchanger by trimeric G‐proteins

Cited by 9 publications

References 51 publications

The Histamine H₃Receptor: Structure, Pharmacology, and Function

The Histamine H₃Receptor: Structure, Pharmacology, and Function

Cardiospecific Overexpression of the Prostaglandin EP ₃ Receptor Attenuates Ischemia-Induced Myocardial Injury

Histaminergic regulation of food intake

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Negative regulation of the platelet Na+/H+ exchanger by trimeric G‐proteins

Cited by 9 publications

References 51 publications

The Histamine H3Receptor: Structure, Pharmacology, and Function

The Histamine H3Receptor: Structure, Pharmacology, and Function

Cardiospecific Overexpression of the Prostaglandin EP 3 Receptor Attenuates Ischemia-Induced Myocardial Injury

Histaminergic regulation of food intake

Contact Info

Product

Resources

About

Negative regulation of the platelet Na⁺/H⁺ exchanger by trimeric G‐proteins

The Histamine H₃Receptor: Structure, Pharmacology, and Function

The Histamine H₃Receptor: Structure, Pharmacology, and Function

Cardiospecific Overexpression of the Prostaglandin EP ₃ Receptor Attenuates Ischemia-Induced Myocardial Injury