Last update 01 Nov 2024

GPR39

Last update 01 Nov 2024

Basic Info

Synonyms

G protein-coupled receptor 39, G-protein coupled receptor 39, GPR39

Introduction

Zn(2+) acts as an agonist. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated mainly through G(q)-alpha and G(12)/G(13) proteins. Involved in regulation of body weight, gastrointestinal mobility, hormone secretion and cell death (By similarity).

Drugs associated with GPR39

GPR39 agonist (Cerevance)

Target

GPR39

Mechanism

GPR39 agonists

Active Org.

Cerevance, Inc.Startup

Originator Org.

Cerevance, Inc.Startup

Active Indication

Parkinson Disease

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with GPR39

100 Translational Medicine associated with GPR39

0 Patents (Medical) associated with GPR39

279

Literatures (Medical) associated with GPR39

01 Nov 2024·Biochemical and Biophysical Research Communications

Cholic acid activation of GPBAR1 does not induce or exacerbate acute pancreatitis but promotes exocrine pancreatic secretion

Article

Author: Du, Ziwei ; Chen, Haiyan ; Fan, Yudan ; Huang, Na ; Zhang, Chen ; Li, Jun ; Wang, Qian ; An, Peng ; Sun, Jin

Obstruction of bile ducts due to gallstones can lead to biliary acute pancreatitis (BAP). According to Perides et al., G protein-coupled bile acid receptor-1 (GPBAR1) mediates BAP. However, Zi's findings suggest that GPR39, rather than GPBAR1, mediates TLCAS-induced increases in cytosolic calcium and acinar cell necrosis, casting doubt on the role of GPBAR1 in BAP. Numerous G protein-coupled receptors on pancreatic acinar cells utilize Ca²⁺ and cyclic adenosine monophosphate (cAMP) as second messengers to manage pancreatic exocrine secretion, with significant cross-talk between these signals. The primary bile acid cholic acid (CA) and its conjugated forms are predominant in the human gallbladder. This study aimed to clarify the role and physiological significance of GPBAR1 by investigating the physiological and pathological effects of CA activation on GPBAR1 in pancreatic acinar cells. Isolated rat pancreatic acinar cells were treated with CA and CCK in vitro to observe the effect of CA-induced cAMP signaling on CCK-induced physiological and pathological calcium signaling. In vivo evaluations involved reverse biliopancreatic duct injections of 5 % sodium taurocholate (STC) or 5 % CA in rats. CA induced intracellular cAMP signaling in a concentration-dependent manner without increasing the intracellular Ca²⁺ concentration. CA did not independently cause calcium overload or enzyme activation, nor did it exacerbate calcium overload or enzyme activation from high-dose CCK. Reverse biliopancreatic duct injections of 5 % CA did not cause acute pancreatitis in the rats. Transcriptomic analysis revealed that 50 μM CA induced changes in gene expression related to protein synthesis in the endoplasmic reticulum and ribosomes. Furthermore, 50 μM CA accelerated the calcium waves and increased the enzyme secretion induced by CCK. GPBAR1 was found on the basolateral membrane in rat pancreatic tissue rather than near the apical region of acinar cells. GPBAR1 activation is not crucial for BAP activity but may play a role in bile acid regulation of pancreatic exocrine secretion, suggesting that GPBAR1 is a potential therapeutic target for pancreatic exocrine insufficiency.

01 Oct 2024·Journal of Molecular and Cellular Cardiology

Zinc attenuates monocrotaline-induced pulmonary hypertension in rats through upregulation of A20

Article

Author: Chen, Ai ; Liu, Junping ; Chen, Weixiao ; Wu, Jingying ; Gao, Gufeng ; Xie, Liangdi ; Lian, Guili ; Yan, Yan

Pulmonary hypertension (PH) is characterized by excessive proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs), in which inflammatory signaling caused by activation of the NF-κB pathway plays an important role. A20 is an important negative regulator of the NF-κB pathway, and zinc promotes the expression of A20 and exerts a protective effect against various diseases (e.g. COVID19) by inhibiting the inflammatory signaling. The role of A20 and intracellular zinc signaling in PH has been explored, but the extracellular zinc signaling is not well understood, and whether zinc has protective effects on PH is still elusive. Using inductively coupled plasma mass spectrometry (ICP-MS), we studied the alteration of trace elements during the progression of monocrotaline (MCT)-induced PH and found that serum zinc concentration was decreased with the onset of PH accompanied by abnormalities of other three elements, including copper, chromium, and magnesium. Zinc chloride injection with the dosage of 5 mg/kg intraperitoneally partially corrected this abnormality and inhibited the progression of PH. Zinc supplementation induced the expression of A20 in lung tissue and reduce the inflammatory responses. In vitro, zinc supplementation time-dependently upregulated the expression of A20 in PASMCs, therefore correcting the excessive proliferation and migration of cells caused by hypoxia. Using genetically encoded-FRET based zinc probe, we found that these effects of zinc ions are not achieved by entering cells, but most likely by activating cell surface zinc receptor (ZnR/GPR39). These results provide the first evidence of the effectiveness of zinc supplementation in the treatment of PH.

01 Sep 2024·European Journal of Pharmacology

Role of orphan G-protein coupled receptors in tissue ischemia: A comprehensive review

Review

Author: Keifi Bajestani, Alireza ; Alavi, Mohaddeseh Sadat ; Etemad, Leila ; Roohbakhsh, Ali

Ischemic events lead to many diseases and deaths worldwide. Ischemia/reperfusion (I/R) occurs due to reduced blood circulation in tissues followed by blood reflow. Reoxygenation of ischemic tissues is characterized by oxidative stress, inflammation, energy distress, and endoplasmic reticulum stress. There are still no adequate clinical protocols or pharmacological approaches to address the consequences of I/R damage. G protein-coupled receptors (GPCRs) are important therapeutic targets. They compose a large family of seven transmembrane-spanning proteins that are involved in many biological functions. Orphan GPCRs are a large subgroup of these receptors expressed in different organs. In the present review, we summarized the literature regarding the role of orphan GPCRs in I/R in different organs. We focused on the effect of these receptors on modulating cellular and molecular processes underlying ischemia including apoptosis, inflammation, and autophagy. The study showed that GPR3, GPR4, GPR17, GPR30, GPR31, GPR35, GPR37, GPR39, GPR55, GPR65, GPR68, GPR75, GPR81, and GPR91 are involved in ischemic events, mainly in the brain and heart. These receptors offer new possibilities for treating I/R injuries in the body.

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GPR39

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