Histamine Receptors: Ex Vivo Functional Studies Enabling the Discovery of Hits and Pathways

Abstract

Histamine receptors (HRs) are G-protein-coupled receptors involved in diverse responses triggered by histamine release during inflammation or by encounters with venomous creatures. Four histamine receptors (H1R–H4R) have been cloned and extensively characterized. These receptors are distributed throughout the body and their activation is associated with clinical manifestations such as urticaria (H1R), gastric acid stimulation (H2R), regulation of neurotransmitters in neuronal diseases (H3R), and immune responses (H4R). Despite significant homologous overlap between H3R and H4R, much remains unknown about their precise roles. Even though some drugs have been developed for H1R, H2R, and H3R, not a single H4R antagonist has been approved for clinical use. To enhance our understanding and advance innovative therapeutic targeting of H1R, H2R, H3R, and H4R, we established a robust ex vivo functional platform. This platform features the successful heterologous expression of H1R–H4R in Xenopus laevis oocytes, utilizing an electrophysiological readout. Our findings contribute to a deeper understanding of the function and pharmacological properties of the histamine receptors. Researchers can benefit from the utility of this platform when investigating the effects of histamine receptors and exploring potential therapeutic targets. In doing so, it broadens the horizon of drug discovery, offering new perspectives for therapeutic interventions.

The Sobering Sting: Oleoyl Serotonin Is a Novel Stephanoconus Snail Venom-Derived Antagonist of Cannabinoid Receptors That Counteracts Learning and Memory Deficits

“…Regarding the structure, OS (Figure 1A) shares a similar structure with AEA (a partial agonist of CB1 receptors) and Org27569 (a positive allosteric modulator of CB1 receptors in binding, a negative allosteric modulator of CB1 receptors in function) (Figure S1), which indicates that it may act through CB receptors and, as seen in other studies that modulated CB receptors' function, affect behavior and memory [1][2][3]. Venoms can be seen as an untapped source of molecules that can be highly selective and potent ligands for a wide range of ion channels and receptors [27,28]. In the present study, we evaluated the effects of an endocannabinoid-like molecule found in cone snail venom.…”

An Investigation of Anti-inflammatory Effects of Famotidine in Rats by Evaluating Inflammatory Cells and Lung Histopathology: An Airway Model

“…Its widespread use by millions of patients worldwide further supports its safety profile (Brennan et al, 2022). Histamine triggers the activation of protein kinase A, resulting in the (H+/K+) activation, which ultimately leads to elevated secretion of gastric acid (Seldeslachts et al, 2023). The H2R, which famotidine targets, extends beyond the stomach and is also present in other anatomical regions, including the pulmonary system (Mukherjee et al, 2021).…”