Dear Colleagues,

G protein-coupled receptors (GPCRs) are seven-transmembrane receptors and form the largest family of membrane receptors and are categorized into six classes based on sequence and function. They respond to diverse stimuli like photons, odors, pheromones, hormones, neurotransmitters, growth factors, and inflammatory mediators. GPCRs amplify cell surface signals by activating heterotrimeric G proteins, which in turn activate several effectors that produce the second messenger and amplify downstream signaling. This ability to amplify the message contributes to their significant role in many physiological pathways, dysregulation of which contribute to many diseases. This type of signal amplification also allows them to be good drug targets.

The physiological role of GPCRs in the cardiovascular system involves the regulation of myocardial contraction, arterial resistance, and renal function. A variety of GPCRs control the tone in smooth muscle from the airway and blood vessels and maintain platelet function. In cardiac pathology, they have a role in promoting hypertrophy, inflammation, and heart failure. In vascular diseases, the contribution seems overwhelming, including atherosclerosis, pulmonary hypertension, hypertension, and aneurysm and thrombosis. GPCRs play a critical role in insulin release and pancreatic beta-cell survival. In type 2 diabetes, GPCRs control adipocyte metabolism and inflammation, in turn controlling insulin resistance in liver and skeletal muscle and metabolic syndrome.

GPCRs ligands control inflammation and regulate both innate and adaptive immune responses. Ligands for these receptors include chemokines, lipid mediators, nucleosides, and inflammatory peptides. GPCRs trigger signaling pathways that facilitate the release of antimicrobial mediators from leukocytes and secondarily induce expression of additional chemokines and cytokines that amplify, extend, or terminate immune responses. Chemokine receptors on neutrophils macrophages and T cells are essential for migration and adhesion. Macrophages express several GPCRs that are involved in differentiation and polarization. In septic shock, GPCRs mediate acute lung injury, kidney injury, and neuronal injury due to pathogens. Recruitment of macrophages to tumors in breast, lung, intestinal, and brain cancers involve GPCRs.

GPCRs ligands play an important role in controlling synaptic transmission and in transmitter release in the nervous system. They also have a pathological role in neuropsychiatric disorders, such as bipolar disease and schizophrenia, and neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s.

Given their role in the various physiological process, including growth, metabolism, inflammation, GPCRs are essential in maintaining homeostasis. Many GPCRs also contribute to the pathophysiology of many diseases and have been targeted by the drug industry. The advantages of the use of biased GPCR agonists can maximize clinical effectiveness while minimizing side effects. The majority of the drugs are approved for the treatment in cardiovascular diseases, CNS, asthma, allergies target GPCRs, with many newer ones still in clinical trials. Therefore, the understanding of the role that GPCRs play in physiology and pathology in different tissues and diseases may lead to better drug targets. The objective of this Special Issue is to gather the newest results and advances on the role of GPCRs in physiology and pathology.

Dr. Vijaya Karoor
Guest Editor

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• GPCR
• cardiovascular
• Alzheimer’s
• Parkinson’s
• inflammation
• thrombosis