October 2022 "Systolic heart failure (HF) is a chronic clinical syndrome characterized by the reduction in cardiac function and still remains the disease with the highest mortality worldwide. Despite considerable advances in pharmacological treatment, HF represents a severe clinical and social burden. Chronic human HF is characterized by several important neurohormonal perturbations, emanating from both the autonomic nervous system and the adrenal glands. Circulating catecholamines (norepinephrine and epinephrine) and aldosterone elevations are among the salient alterations that confer significant hormonal burden on the already compromised function of the failing heart. This is why sympatholytic treatments (such as β-blockers) and renin-angiotensin system inhibitors or mineralocorticoid receptor antagonists, which block the effects of angiotensin II (AngII) and aldosterone on the failing heart, are part of the mainstay HF pharmacotherapy presently. The adrenal gland plays an important role in the modulation of cardiac neurohormonal stress because it is the source of almost all aldosterone, of all epinephrine, and of a significant amount of norepinephrine reaching the failing myocardium from the blood circulation. Synthesis and release of these hormones in the adrenals is tightly regulated by adrenal G protein-coupled receptors (GPCRs), such as adrenergic receptors and AngII receptors. In this review, we discuss important aspects of adrenal GPCR signaling and regulation, as they pertain to modulation of cardiac function in the context of chronic HF, by focusing on the 2 best studied adrenal GPCR types in that context, adrenergic receptors and AngII receptors (AT 1 Rs). Particular emphasis is given to findings from the past decade and a half that highlight the emerging roles of the GPCR-kinases and the β-arrestins in the adrenals, 2 protein families that regulate the signaling and functioning of GPCRs in all tissues, including the myocardium and the adrenal gland." Read more at the source #DrGPCR #GPCR #IndustryNews

September 2022 Regulator of G Protein Signaling 20 Correlates with Long Intergenic Non-Coding RNA (lincRNAs ; (d) RGS20 was found to be significantly associated with some tumor-related signaling pathways and long

detection, receptor activation initiates conformational changes, exposing an intracellular cavity (Kang recognized for inhibiting G protein signaling, they also influence specific pathways such as MAPK signaling (Song Despite multifocal signaling, recent studies indicate that signaling occurs within a 100 nm range from high-resolution protein structures, illuminating side chain orientations and overall conformational states (Kang , as well as MAPK cascade kinases which can be activated through specific β-arrestin conformations (Song

What mariachi song are you most likely to shout along to at 3 AM? Mariachi song: I typically do not sing to these since they are dear to Mexican childhood memories, and Don’t be surprised if you find yourself singing Daddy Yankee’s “Gasolina” from the top of your lungs

disease before they can even dare to contemplate the development of therapeutic options and begin the long Modern drug development approaches include a range of techniques leveraging structural biology, immunology

We show that besides classical hydrogen bonds, weak polar interactions such as O-HC, O-Br, and long-range

Artificial intelligence - Machine learning vs Deep Learning GPCRs have long been recognized as important to predict subtype-selective ligands for dopamine receptors and adenosine receptors (He, Ben, Kuang, Wang & Kong, 2016; Kuang, Feng, Hu, Wang, He & Kong, 2016). 5. ability of a ligand to induce or inhibit a cellular response (pEC50 or pIC50, respectively), and how long

Our results reveal that the extended N-terminus of the long isoform limits G protein activation yet elevates constitutive G13 activation, while an additional cysteine contributed by the extended N-terminus of the long

GPCRs have been long considered as controllers of communication between tissues and cells. receptorsomes, both at the cell surface membrane and in the intracellular domain dictate and condition long-term

Here, we investigate the effects that long-term CNO stimulatory culture have on hM3Dq [Ca2+]i signaling Long-term culturing under repeated CNO stimulation modified the temporal dynamics of hM3Dq [Ca2+]i signaling

adopted to elucidate the structure, pharmacology, and signaling of cardiovascular GPCRs, resolving long-standing

Sir William Osler Scientists have long sought to discover a “golden bullet” that would cure every disease signal-regulated kinases (ERK), a subset of the mitogen-activated protein kinase (MAPK) family, have long

heterogeneous disease with few effective targeted therapies and precision therapeutic options over a long

The study reports that human white blood cells express an average of 160 GPCR mRNAs, ranging from 123 the insights gained from this research will be instrumental in shaping therapeutic strategies for a range

August 2022 "Despite the importance of members of the GPCR superfamily as targets of a broad range of Expression of GPR84 is strongly up regulated in immune cells in a range of pro-inflammatory settings

In addition to the RGS domain, RGS proteins also contain a range of other structural motifs that are : Recent studies have revealed that the interaction between RGS proteins and GPCRs is mediated by a range of RGS protein dysregulation in disease: The Dysregulation of RGS proteins has been implicated in a range The dysregulation of these proteins has been implicated in a range of diseases, and understanding the Wang, Q., L.Y. Liu-Chen, and J.R.

well as target validation strategies for the discovery and development of novel therapeutic agents ranging

this review, we have compared expression of GPCR mRNAs in human islets obtained from normal weight range donors, and those with a weight range classified as obese.

March 2022 "February 17, 2022 08:00 AM Eastern Standard Time SAN FRANCISCO & SHANGHAI- ShouTi Inc., clinical-stage global biopharmaceutical company developing novel oral therapeutics to treat a wide range

develop a deep pipeline of novel, targeted, nonpeptide radiopharmaceuticals for the treatment of a broad range Against 10 Oncology Targets – Radionetics and Crinetics to Collaborate on Multiple Additional targets SAN develop a deep pipeline of novel, targeted, nonpeptide radiopharmaceuticals for the treatment of a broad range

Adrenomedullin 2/intermedin is a slow off-rate, long-acting endogenous agonist of the adrenomedullin2

., Glucagon-Like Peptide-1 and Its Class B G Protein-Coupled Receptors: A Long March to Therapeutic Successes

cytokines along with their receptors, are involved in various biologic processes and regulation of a wide range

recent years as researchers have discovered the vast potential for GPCR-targeting drugs in treating a range

"G protein-coupled receptors (GPCRs) are of considerable interest due to their importance in a wide range

pyrimidines as Tools to Investigate A3 Adenosine Receptors in Cancer Cell Lines Severity of neurological long-COVID

GRK2/β-arrestin2 play multiple roles in the pathological mechanisms of a wide range of diseases including

candidate into clinical trials " HTL0039732 is a novel EP4 antagonist with potential to treat a wide range