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CGMP: a unique 2nd messenger molecule - recent developments in cGMP research and development.

ABSTRACT: Cyclic guanosine monophosphate (cGMP) is a unique second messenger molecule formed in different cell types and tissues. cGMP targets a variety of downstream effector molecules and, thus, elicits a very broad variety of cellular effects. Its production is triggered by stimulation of either soluble guanylyl cyclase (sGC) or particulate guanylyl cyclase (pGC); both enzymes exist in different isoforms. cGMP-induced effects are regulated by endogenous receptor ligands such as nitric oxide (NO) and natriuretic peptides (NPs). Depending on the distribution of sGC and pGC and the formation of ligands, this pathway regulates not only the cardiovascular system but also the kidney, lung, liver, and brain function; in addition, the cGMP pathway is involved in the pathogenesis of fibrosis, inflammation, or neurodegeneration and may also play a role in infectious diseases such as malaria. Moreover, new pharmacological approaches are being developed which target sGC- and pGC-dependent pathways for the treatment of various diseases. Therefore, it is of key interest to understand this pathway from scratch, beginning with the molecular basis of cGMP generation, the structure and function of both guanylyl cyclases and cGMP downstream targets; research efforts also focus on the subsequent signaling cascades, their potential crosstalk, and also the translational and, ultimately, the clinical implications of cGMP modulation. This review tries to summarize the contributions to the "9th International cGMP Conference on cGMP Generators, Effectors and Therapeutic Implications" held in Mainz in 2019. Presented data will be discussed and extended also in light of recent landmark findings and ongoing activities in the field of preclinical and clinical cGMP research.

SUBMITTER: Friebe A

PROVIDER: S-EPMC7260148 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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cGMP: a unique 2nd messenger molecule - recent developments in cGMP research and development.

Friebe Andreas A Sandner Peter P Schmidtko Achim A

Naunyn-Schmiedeberg's archives of pharmacology 20191218 2

Cyclic guanosine monophosphate (cGMP) is a unique second messenger molecule formed in different cell types and tissues. cGMP targets a variety of downstream effector molecules and, thus, elicits a very broad variety of cellular effects. Its production is triggered by stimulation of either soluble guanylyl cyclase (sGC) or particulate guanylyl cyclase (pGC); both enzymes exist in different isoforms. cGMP-induced effects are regulated by endogenous receptor ligands such as nitric oxide (NO) and na ...[more]

PMID: 31853617

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Project description:IntroductionBurn injury and its subsequent multisystem effects are commonly encountered by acute care practitioners. Resuscitation is the major component of initial burn care and must be managed to restore and preserve remote organ function. Later complications of burn injury are dominated by infection. Burn centers are often called to manage soft tissue problems outside thermal injury including soft tissue infection and Toxic Epidermal Necrolysis.MethodsA selected review of recent reports published by the American Burn Association is provided.ResultsThe burn-injured patient is easily and frequently over resuscitated with complications including delayed wound healing and respiratory compromise. A feedback protocol is designed to limit the occurrence of excessive resuscitation has been proposed but no new "gold standard" for resuscitation has replaced the Parkland formula. Significant additional work has been included in recent guidelines identifying specific infectious complications and criteria for these diagnoses in the burn-injured patient. While new medical therapies have been proposed for patients sustaining inhalation injury, a new standard of medical therapy has not emerged. Renal failure as a contributor to adverse outcome in burns has been reinforced by recent data generated in Scandinavia. Of special problems addressed in burn centers, soft tissue infections and Toxic Epidermal Necrolysis have been reviewed but new treatment strategies have not been identified. The value of burn centers in management of burns and other soft tissue problems is supported in several recent reports.ConclusionRecent reports emphasize the dangers of over resuscitation in the setting of burn injury. No new medical therapy for inhalation injury exists but new standards for description of burn-related infections have been presented. The value of the burn center in care of soft tissue problems including Toxic Epidermal Necrolysis and soft tissue infections is supported in recent papers.

Dataset Information

CGMP: a unique 2nd messenger molecule - recent developments in cGMP research and development.

Publications

cGMP: a unique 2nd messenger molecule - recent developments in cGMP research and development.

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