Investigation of receptor binding and functional characteristics of hemopressin(1–7)

Dvorácskó, Szabolcs; Tömböly, Csaba; Berkecz, Róbert; Keresztes, Attila

doi:10.1016/j.npep.2016.02.001

Cited by 17 publications

(7 citation statements)

References 41 publications

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“…Dvorácskó et al . recently reported that a truncated hemopressin peptide (PVNFKFL, Hp(1‐7)), a related family member of pepcan‐12, could act as an allosteric ligand or indirect regulator of the endocannabinoid system rather than an endogenous ligand as postulated previously.…”

Section: Negative Allosteric Modulators (Nams) Of the Cb1 Receptormentioning

confidence: 74%

Allosteric Modulation: An Alternate Approach Targeting the Cannabinoid CB1 Receptor

Nguyễn

Thomas

et al. 2016

Medicinal Research Reviews

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The cannabinoid CB1 receptor is a G protein-coupled receptor and plays an important role in many biological processes and physiological functions. A variety of CB1 receptor agonists and antagonists, including endocannabinoids, phytocannabinoids and synthetic cannabinoids have been discovered or developed over the past 20 years. In 2005 it was discovered that the CB1 receptor contains allosteric site(s) which can be recognized by small molecules, or allosteric modulators. A number of CB1 receptor allosteric modulators, both positive and negative, have since been reported and importantly, they display pharmacological characteristics that are distinct from those of orthosteric agonists and antagonists. Given the psychoactive effects commonly associated with CB1 receptor agonists and antagonists/inverse agonists, allosteric modulation may offer an alternate approach to attain potential therapeutic benefits while avoiding inherent side effects of orthosteric ligands. This review details the complex pharmacological profiles of these allosteric modulators, their structure-activity relationships, and efforts in elucidating binding modes and mechanisms of actions of reported CB1 allosteric modulators. The ultimate development of CB1 receptor allosteric ligands could potentially lead to improved therapies for CB1-mediated neurological disorders.

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Section: Negative Allosteric Modulators (Nams) Of the Cb1 Receptormentioning

confidence: 74%

Allosteric Modulation: An Alternate Approach Targeting the Cannabinoid CB1 Receptor

Nguyễn

Thomas

et al. 2016

Medicinal Research Reviews

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“…Others have also failed to find evidence for hemopressin activity at the CB1 receptor. [35][36][37] We therefore turned our attention to the natural plant-derived CBD. CBD has a low affinity for the CB1 receptor and functions as a noncompetitive allosteric antagonist.…”

Section: Discussionmentioning

confidence: 99%

2-Linoleoylglycerol Is a Partial Agonist of the Human Cannabinoid Type 1 Receptor that Can Suppress 2-Arachidonolyglycerol and Anandamide Activity

Williams

Doherty

2019

Cannabis and Cannabinoid Research

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Introduction: The cannabinoid type 1 (CB1) receptor and cannabinoid type 2 (CB2) receptor are widely expressed in the body and anandamide (AEA) and 2-arachidonoylglycerol (2-AG) are their best characterized endogenous ligands. The diacylglycerol lipases (diacylglycerol lipase alpha and diacylglycerol lipase beta) not only synthesize essentially all the 2-AG in the body but also generate other monoacylglycerols, including 2linoleoylglycerol (2-LG). This lipid has been proposed to modulate endocannabinoid (eCB) signaling by protecting 2-AG from hydrolysis. However, more recently, 2-LG has been reported to be a CB1 antagonist. Methods: The effect of 2-LG on the human CB1 receptor activity was evaluated in vitro using a cell-based reporter assay that couples CB1 receptor activation to the expression of the b-lactamase enzyme. Receptor activity can then be measured by a b-lactamase enzymatic assay. Results: When benchmarked against 2-AG, AEA, and arachidonoyl-2¢-chloroethylamide (a synthetic CB1 agonist), 2-LG functions as a partial agonist at the CB1 receptor. The 2-LG response was potentiated by JZL195, a drug that inhibits the hydrolysis of monoacylglycerols. The 2-LG response was also fully inhibited by the synthetic CB1 antagonist AM251 and by the natural plant derived antagonist cannabidiol. 2-LG did not potentiate, and only blunted, the activity of 2-AG and AEA. Conclusions: These results support the hypothesis that 2-LG is a partial agonist at the human CB1 receptor and capable of modulating the activity of the established eCBs.

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“…Hp was originally identified as an inverse agonist/antagonist of CB1 [ 154 ]. A few years ago, a study revealed that Hp slightly activated G proteins and functioned as a very weak agonist, proposing a hypothesis that Hp indirectly interacts with CB1 [ 155 ]. In addition, it is confirmed that Hp does not function as a NAM of CB1 in a study using electrophysiology [ 156 ].…”

Section: Novel Cannabinoids From Animal Sourcesmentioning

confidence: 99%

Targeting Cannabinoid Receptors: Current Status and Prospects of Natural Products

Peigneur

Hendrickx

et al. 2020

IJMS

131

114

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Cannabinoid receptors (CB1 and CB2), as part of the endocannabinoid system, play a critical role in numerous human physiological and pathological conditions. Thus, considerable efforts have been made to develop ligands for CB1 and CB2, resulting in hundreds of phyto- and synthetic cannabinoids which have shown varying affinities relevant for the treatment of various diseases. However, only a few of these ligands are clinically used. Recently, more detailed structural information for cannabinoid receptors was revealed thanks to the powerfulness of cryo-electron microscopy, which now can accelerate structure-based drug discovery. At the same time, novel peptide-type cannabinoids from animal sources have arrived at the scene, with their potential in vivo therapeutic effects in relation to cannabinoid receptors. From a natural products perspective, it is expected that more novel cannabinoids will be discovered and forecasted as promising drug leads from diverse natural sources and species, such as animal venoms which constitute a true pharmacopeia of toxins modulating diverse targets, including voltage- and ligand-gated ion channels, G protein-coupled receptors such as CB1 and CB2, with astonishing affinity and selectivity. Therefore, it is believed that discovering novel cannabinoids starting from studying the biodiversity of the species living on planet earth is an uncharted territory.

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Investigation of receptor binding and functional characteristics of hemopressin(1–7)

Cited by 17 publications

References 41 publications

Allosteric Modulation: An Alternate Approach Targeting the Cannabinoid CB1 Receptor

Allosteric Modulation: An Alternate Approach Targeting the Cannabinoid CB1 Receptor

2-Linoleoylglycerol Is a Partial Agonist of the Human Cannabinoid Type 1 Receptor that Can Suppress 2-Arachidonolyglycerol and Anandamide Activity

Targeting Cannabinoid Receptors: Current Status and Prospects of Natural Products

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