Handbook of experimental pharmacology最新文献_第4页

The Role of Hydrogen Sulfide in Peripheral Nervous System Modulation. 硫化氢在周围神经系统调节中的作用。

Handbook of experimental pharmacology Pub Date : 2026-01-01 DOI: 10.1007/164_2025_777

Saúl Huerta de la Cruz, Diana L Silva-Velasco, Jesus H Beltran-Ornelas, David Centurión

{"title":"The Role of Hydrogen Sulfide in Peripheral Nervous System Modulation.","authors":"Saúl Huerta de la Cruz, Diana L Silva-Velasco, Jesus H Beltran-Ornelas, David Centurión","doi":"10.1007/164_2025_777","DOIUrl":"10.1007/164_2025_777","url":null,"abstract":"Hydrogen sulfide (H2S) is a gasotransmitter that contributes to the regulation of peripheral nervous system (PNS) function. H2S is produced by several enzymes whose expression changes under different physiological and pathological conditions, influencing how peripheral neurons respond to environmental and internal signals. H2S modulates neuronal excitability through its actions on ion channels and through interactions with other gasotransmitters, shaping sensory, autonomic, and pain-related pathways. In autonomic circuits, H2S adjusts sympathetic and parasympathetic activity. Through these actions, it affects cardiovascular control, gastrointestinal motility, and respiratory rhythm. In pain pathways, H2S can modulate nociception in either direction, with its effectsshaped by the physiological or pathological state. H2S participates in multiple pain conditions and contributes to changes in peripheral and spinal processing that influence pain sensitivity. Overall, H2S influences several components of peripheral neurobiology and represents a potential target for strategies aimed at treating autonomic dysfunction and chronic pain.","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":"41-64"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145762677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Biased Agonism at β-Adrenoceptor Subtypes: A Drug Development Perspective. β-肾上腺素能受体亚型的偏向激动作用：药物开发的观点。

Handbook of experimental pharmacology Pub Date : 2026-01-01 DOI: 10.1007/164_2025_769

Martin C Michel, Ongun Onaran

{"title":"Biased Agonism at β-Adrenoceptor Subtypes: A Drug Development Perspective.","authors":"Martin C Michel, Ongun Onaran","doi":"10.1007/164_2025_769","DOIUrl":"10.1007/164_2025_769","url":null,"abstract":"Selectivity of a drug for a desired response as compared to undesirable responses (side effect) is a key goal of drug development. Early concepts to achieve such selectivity were based on selectivity for a molecular target as compared to others, pharmacokinetic factors to achieve high concentrations in the target tissue as compared to low concentrations in others, differential efficacy in the target vs. others tissues, and leveraging the concept of cell type and tissue differences in expression levels of receptors and their related signaling molecules, which can be further complicated by alterations of such ratios in disease. Biased agonism occurs when one response is activated preferentially over another after accounting for the above other factors. Thus, assessment of ligand bias is not always easy. β-Adrenoceptors have played a relevant role in our understanding of the phenomenon of biased agonism. Several clinically used β-adrenoceptor ligands were proposed to exhibit biased agonism, but the findings often are inconclusive, at least partly based on the overall complexity of assessment of biased signaling. These complexities also make it challenging to determine the desired biased profile of a ligand at the start of a drug research and development project, particularly for innovative applications. Thus, biased agonism has potential to contribute to functional target selectivity, but its prospective use remains challenging.","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":"203-219"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

H₂S Signaling and SKM Physiopathology. H2S信号和SKM生理病理。

Handbook of experimental pharmacology Pub Date : 2026-01-01 DOI: 10.1007/164_2025_779

Valentina Vellecco, Martina Smimmo, Veronica Casale, Mariarosaria Bucci

引用次数: 0

GPCR Biased Signaling in Cancer. 肿瘤中GPCR偏倚信号传导。

Handbook of experimental pharmacology Pub Date : 2026-01-01 DOI: 10.1007/164_2025_773

Ariella C Avigad, Melody Zhou, Chengyu Sun, Levin Ma, Xue Li, Rosie J Blodgett, Vera S Donnenberg, Albert D Donnenberg, Patrick L Wagner, David L Bartlett, Kunhong Xiao

{"title":"GPCR Biased Signaling in Cancer.","authors":"Ariella C Avigad, Melody Zhou, Chengyu Sun, Levin Ma, Xue Li, Rosie J Blodgett, Vera S Donnenberg, Albert D Donnenberg, Patrick L Wagner, David L Bartlett, Kunhong Xiao","doi":"10.1007/164_2025_773","DOIUrl":"10.1007/164_2025_773","url":null,"abstract":"G protein-coupled receptors (GPCRs) represent the largest family of cell surface receptors. They orchestrate various signaling pathways, playing a central role in regulating various physiological and pathophysiological processes. Dysregulation of GPCR signaling has been intricately linked to cancer pathogenesis, including tumor growth, angiogenesis, metastasis, and immune modulation. Biased GPCR signaling occurs when a ligand preferentially activates one signaling pathway over another, leading to distinct cellular outcomes. In cancer, biased GPCR signaling represents a complex, dynamic phenomenon, significantly influencing cancer development, progression, and treatment resistance. This chapter reviews recent advances in our understanding of GPCR biased signaling in various aspects of cancer biology and explores its therapeutic potential. Given the fragmented nature of existing evidence, we integrate available literature with findings from our own proteomics studies on GPCR and β-arrestin function to provide a preliminary framework for understanding β-arrestin-mediated signaling in cancer. While this overview may capture only a limited snapshot of the broader landscape, it provides a valuable foundation for generating new hypotheses and guiding future research and drug discovery efforts in oncology.","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":"277-318"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145400651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Role of Hydrogen Sulfide-Derived Perivascular Adipose Tissue in Vascular Diseases. 硫化氢衍生的血管周围脂肪组织在血管疾病中的作用。

Handbook of experimental pharmacology Pub Date : 2026-01-01 DOI: 10.1007/164_2025_755

Emma Mitidieri, Chiara Indolfi, Vincenzo Brancaleone, Raffaella Sorrentino, Roberta d'Emmanuele di Villa Bianca

{"title":"The Role of Hydrogen Sulfide-Derived Perivascular Adipose Tissue in Vascular Diseases.","authors":"Emma Mitidieri, Chiara Indolfi, Vincenzo Brancaleone, Raffaella Sorrentino, Roberta d'Emmanuele di Villa Bianca","doi":"10.1007/164_2025_755","DOIUrl":"10.1007/164_2025_755","url":null,"abstract":"Perivascular adipose tissue (PVAT) is a metabolically active, endocrine organ that plays a crucial role in regulating blood vessel tone, endothelial function, vascular smooth muscle cell growth, and proliferation and contributes significantly to the onset and progression of cardiovascular diseases. In a healthy state, PVAT displays anticontractile, anti-inflammatory, and antioxidative properties, which are critical for maintaining vascular homeostasis. However, under certain pathophysiological conditions, PVAT exerts pro-contractile effects by decreasing the production of anticontractile and/or increasing that of pro-contractile factors. In this context, recent studies have identified hydrogen sulfide (H2S) as a key vascular anti-contractile factor released from PVAT. The enzymes responsible for H2S biosynthesis are differentially expressed in PVAT, depending on the vascular bed and species, and their function can be altered by metabolic and cardiovascular diseases. These alterations can influence H2S signalling, further contributing to vascular dysfunction. PVAT-derived H2S may have particular importance in obesity-related vascular disease, hypertension, and diabetes as it has direct paracrine effects on the vasculature. Understanding the role of PVAT-derived H2S in both healthy and diseased states may provide new insights into preventing vascular dysfunction associated with PVAT changes. The dissection of the specific contributions of each enzyme involved in PVAT-derived H2S biosynthesis could be relevant to fully understanding the complex role of H2S in vascular health vs vascular disease. Further research into modulating PVAT-derived H2S provides an exciting avenue to explore novel pharmacological targets against vascular disease pathogenesis.","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":"123-146"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145291970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Antiplatelet Therapy. 抗血小板治疗。

Handbook of experimental pharmacology Pub Date : 2026-01-01 DOI: 10.1007/164_2025_784

Richard T Amison, Simon C Pitchford

引用次数: 0

Correction to: The Role of H2S in Atherosclerosis and Associated Cardiometabolic Comorbidities. 修正：H2S在动脉粥样硬化和相关心脏代谢合并症中的作用。

Handbook of experimental pharmacology Pub Date : 2026-01-01 DOI: 10.1007/164_2026_795

Odysseia Savvoulidou, Turtushikh Damba, Daniel F J Ketelhuth, Maria Peleli

引用次数: 0

Hydrogen Sulfide in Adipose Tissue Biology. 硫化氢在脂肪组织生物学中的应用。

Handbook of experimental pharmacology Pub Date : 2026-01-01 DOI: 10.1007/164_2025_759

Antonia Katsouda, Andreas Papapetropoulos

引用次数: 0

GPCR Phospho-Barcodes and Biased Signaling. GPCR磷酸化条形码和偏置信号。

Handbook of experimental pharmacology Pub Date : 2026-01-01 DOI: 10.1007/164_2025_761

Qingtao He, Jinpeng Sun, Shenming Huang

引用次数: 0

Mechanisms of Location Bias in G Protein-Coupled Receptors. G蛋白偶联受体定位偏倚的机制。

Handbook of experimental pharmacology Pub Date : 2026-01-01 DOI: 10.1007/164_2025_764

Uyen Pham, Anand Chundi, Sudarshan Rajagopal

引用次数: 0