The Involvement of Adenylyl Cyclase And Cyclic Amp-Dependent Protein Kinases in Luteinizing Hormone Actions
Mario Ascoli in Luteinizing Hormone Action and Receptors, 2019
In this chapter we will review structural and functional aspects that regulate cyclic AMP formation by the enzyme adenylyl cyclase and how cyclic AMP generated as a consequence of hormonal stimulation of adenylyl cyclase regulates the cellular response. With respect to the first of the two main areas to be covered, we will discuss the basic structure and regulation of adenylyl cyclase by nucleotides and Mg, we will speculate on several aspects of activity regulation of the signal-transducing proteins that couple receptors to the adenylyl cyclase proper, and we shall analyze what is known about the regulation of the hormone-receptor interaction by the coupling proteins and what might be learned from it. As applied specifically to LH receptors, we will discuss possible mechanisms involved in the turn-off mechanism that is alternative to hormone dissociation from the system, i.e., desensitization processes. With respect to the second of the areas to be covered, we will review the evidence that exists that cyclic AMP, acting via protein kinase activation and subsequent protein phosphorylation, mediates in a physiologically meaning way steroidogenesis in LH target cells. Finally, we will address the question as to how intracellular specificity of the second messenger cyclic AMP is thought to be achieved.
Secretion, Alveolar Processing, and Turnover of Pulmonary Surfactant
Jacques R. Bourbon in Pulmonary Surfactant: Biochemical, Functional, Regulatory, and Clinical Concepts, 2019
The intracellular mechanisms (i.e., the nature of second messengers and their effects) which trigger the release of lamellar bodies in vivo are not perfectly known. It appears that several different mechanisms must exist. One involves cyclic adenosine monophosphate (cAMP). Any stimulus capable of increasing cellular levels of cAMP appears to induce surfactant release, and the enhancement of surfactant secretion induced by activation of adrenergic receptors (see Section III.A below) appears to involve the mediation of cAMP.20 Thus, β-agonists cause a rise in cAMP concentration in type II cells,17,21,22 cAMP analogs mimic their effects in stimulating surfactant release,17,21,23 and phosphodiesterase inhibitors potentiate their effects.17,22,23 Cholera toxin was also shown to enhance surfactant secretion through an increase of cellular cAMP.24 Its mechanism of action, although not yet determined, could be somewhat different from that of β-agonists since its effects appeared much later after application of the stimulus.
Changes in Gene Expression During Aging of Mammals
Alvaro Macieira-Coelho in Molecular Basis of Aging, 2017
The FNT mRNA is about 8.0 kb long. Nuclear run-on transcription assay shows that its transcription in the liver is less than 10% of that of albumin.16 Cyclic AMP is known to stimulate the expression of the gene. This is brought about by cAMP binding to trans-acting factors which then bind to the CRE in the promoter. Whether or not the levels of trans-acting factors change with age was studied by using a labeled 25-bp-long (25-mer) synthetic double-stranded DNA (dsDNA) containing the CRE sequence (TGACGTCA). It was incubated with nuclear extract of the liver from 2-, 25-, and 110-week-old male rats, and the number of trans-acting factors that bind to it, and their levels, were assayed by gel mobility shift. Three specific proteins were found to bind to the 25-mer DNA, and their levels were significantly lower in the older rat (Figure 3). The expression of the FNT gene was significantly higher in the young. This is the first report on the role of a promoter in the age-related expression of an important gene that codes for a multifunctional protein. It shows that the lower expression of the FNT gene in the older rat may be due to the decrease in the trans-acting factors that bind to a cis-acting element (CRE) in the promoter, and are required for stimulation of its transcription. Also, conformational changes in the chromatin regions in the promoter, as revealed by DNAase I digestion, may alter the expression of the gene.
Enhanced expression of CD39 and CD73 on T cells in the regulation of anti-tumor immune responses
Published in OncoImmunology, 2020
Ivan Shevchenko, Andreas Mathes, Christopher Groth, Svetlana Karakhanova, Verena Müller, Jochen Utikal, Jens Werner, Alexandr V. Bazhin, Viktor Umansky
Extracellular adenosine has been identified as one of the main immunosuppressive factors in the tumor microenvironment, orchestrating the activity of multiple immune cell subsets.10–13 Acting through specific G-protein-coupled receptors, adenosine exerts inhibitory effects on the effector arm of the immune system, while enhancing the activity of regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSCs).10,11,14 These effects of adenosine are mostly dependent on activation of adenylate cyclase followed by an enhanced production of cyclic AMP (cAMP).14 Adenosine is produced through the two-step hydrolysis of extracellular ATP by the cell-surface ectonucleotidases CD39 and CD73 detected in various populations of immune cells as well as in tumor cells and contributing to the immune suppression in the tumor microenvironment.10–14
Design, synthesis, and biological evaluation of triazole-pyrimidine-methylbenzonitrile derivatives as dual A2A/A2B adenosine receptor antagonists
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Zhi Li, Lijuan Kou, Xinzhen Fu, Zeping Xie, Maolei Xu, Lin Guo, Tiantian Lin, Shizhou Gong, Shumin Zhang, Ming Liu
Adenosine is one of the most important signalling molecules in the human body, and it exerts its effects through G-protein coupled receptors, including A1, A2A, A2B, and A3 adenosine receptors (ARs)1–3. Upon activation by adenosine, A2A AR and A2B AR promote adenylyl cyclase (AC) activation and subsequent cyclic AMP (cAMP) production4,5. Elevated intracellular cAMP in T cells will result in T cell anergy by reducing its proliferation, maturation, cytokine production (e.g., IL-2), and tumour-killing activity6–8. The cell cytotoxicities of natural killer cells, dendritic cells, or macrophages are inhibited by this pathway as well9–11. In the tumour microenvironment (TME), the level of extracellular adenosine is higher than that of normal tissue, leading to immune evasion4,12,13. A2A and A2B ARs are widely considered critical to the immune functions of adenosine. The relevance of A2 receptors in tumour immunotherapy has stimulated the development of various selective antagonists for these receptors14–19.
Noradrenergic gating of long-lasting synaptic potentiation in the hippocampus: from neurobiology to translational biomedicine
Published in Journal of Neurogenetics, 2018
Peter V. Nguyen, Jennifer N. Gelinas
NE acts through G protein-coupled receptors broadly classified as α1-, α2-, β1-, and β2-adrenergic receptors (reviewed by Gelinas & Nguyen, 2007). Hippocampal pyramidal cells and dentate gyrus granule cells express all four receptor subtypes (Guo & Li, 2007; Hillman, Knudson, Carr, Doze, & Porter, 2005; Nicholas, Pieribone, & Hokfelt, 1993). β-ARs signal through activation of Gs-type G proteins, followed by stimulation of adenylyl cyclase and increased production of intracellular cAMP. Cyclic-AMP activates cAMP-dependent protein kinase (PKA) and, indirectly, extracellular signal-regulated protein kinase (ERK) through Rap1 (a GTPase) and B-Raf (a protein kinase) (Schmitt & Stork, 2000). PKA and ERK both have critical roles in long-term memory formation and long-term synaptic plasticity in numerous species and they putatively have key roles in the memory enhancing effects of β-AR activation (Barros et al., 1999; Kandel, 2001; Nguyen & Woo, 2003; Sweatt, 2004).
Related Knowledge Centers
- Adenosine Monophosphate
- Adenylyl Cyclase
- Phosphodiesterase
- Second Messenger System
- Signal Transduction
- Adenosine Triphosphate
- Camp-Dependent Pathway
- Gs Alpha Subunit
- Gi Alpha Subunit
- Hormone