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Comparative Anatomy and Physiology of the Mammalian Eye
Published in David W. Hobson, Dermal and Ocular Toxicology, 2020
The control of the production of aqueous humor appears to be complex and not completely understood. It is suggested that the adenylate cyclase receptor complex is responsible for the formation of cyclic AMP, an intracellular messenger that results in a decrease in aqueous humor production.66 This receptor complex apparently is affected by a number of humoral, neurohumoral, and pharmacologic processes and is the final common pathway in the control of aqueous humor inflow.66
β-Adrenergic Receptor Regulation in Cardiac Disease
Published in Irving H. Zucker, Joseph P. Gilmore, Reflex Control of the Circulation, 2020
Dorothy E. Vatner, Charles J. Homcy, Stephen F. Vatner
The cardiomyopathic failing heart showed similar findings of decreased β-adrenergic receptor density and decreased adenylate cyclase responses to isoproterenol but normal forskolin responsiveness (Denniss et al., 1989). Forskolin acts as a potent activator of adenylate cyclase activity, acting directly on the catalytic unit of adenylate cyclase, but forskolin-mediated stimulation of the cyclase is enhanced in the presence of GSα (Seamon et al., 1981; Clark et al., 1982). In studies by Colucci et al. (1987, 1988), patients with heart failure showed a significant loss of inotropic responsiveness (apparent de-sensitization) to the β-adrenergic agonist dobutamine. Also, chronotropic responsiveness to exercise in patients with heart failure was attenuated in response to isoproterenol infusion (Colucci et al., 1989). A selective loss of β1-adrenergic receptors in heart failure was also identified by Brodde et al. (1986). Conversely, in patients with cardiomyopathy, chronic therapy with a β-adrenergic antagonist resulted in increased β-adrenergic receptor density and improved contractile responses to catecholamines (Heilbrunn et al., 1989).
Neuropeptides and Cell Proliferation
Published in Edwin E. Daniel, Neuropeptide Function in the Gastrointestinal Tract, 2019
The activation of adenylate cyclase leading to increased intracellular levels of cAMP is a common pathway preceding cellular mitogenesis. VIP, acting synergistically with insulin, caused a marked accumulation of cAMP in Swiss 3T3 fibroblasts prior to DNA synthesis.15 This was not accompanied by any change in cytoplasmic Ca2+ or in the amounts of protein kinase C. Similarly, VIP and secretin increased cAMP accumulation by cultured rat Schwann cells, while substance P and somatostatin were without effect.28 It is of interest that the growth-inhibitory actions of VIP on smooth muscle cells were also associated with increased formation of cAMP,14 demonstrating how the same intracellular pathway can be used by a single ligand to induce dramatically opposite biological effects. The ability of substance P and neurokinin A to promote smooth muscle cell replication was accompanied by increased inositol phosphate metabolism and was associated with Ca2+ flux, since calcium and calmodulin inhibitors blocked DNA synthesis.29
Tackling retinal ganglion cell apoptosis in glaucoma: role of adenosine receptors
Published in Expert Opinion on Therapeutic Targets, 2021
The purine, adenosine, was shown to affect cellular functions by regulating the activity of adenylate cyclase as early as in 1970 [5]. Later, its role as a signaling molecule was established. Adenosine is a degradation product of adenosine triphosphate (ATP), which for long time was believed to be an intracellular molecule playing central role in energy metabolism. In 1950s, it was observed that ATP is released along with neurotransmitters and later in 1972 its role in neurotransmission was recognized, and this was followed by the discovery of several classes of purinergic receptors. It is now well established that by modulating neurotransmission in CNS, adenosine plays an important regulatory role in several CNS functions including inflammation, pain, blood flow, sleep wake cycles as well as responses to ischemia [6]. Adenosine is generated intracellularly by the hydrolysis of ATP mainly by neucleotidases and is then transported extracellularly via various transporters. It can also be produced extracellularly by hydrolysis of adenine nucleotides.
Fumarate hydratase as a therapeutic target in renal cancer
Published in Expert Opinion on Therapeutic Targets, 2020
Priyanka Kancherla, Michael Daneshvar, Rebecca A. Sager, Mehdi Mollapour, Gennady Bratslavsky
Identifying synthetic lethality with FH in other cellular pathways may also highlight other therapeutic targets. To that end, Boettcher et al. performed an RNA-based screen of 10,000 genes to identify those that demonstrate synthetic lethality with FH [79]. Their screen confirmed synthetic lethality of heme oxygenase as demonstrated by Frezza et al. [75]. Additionally, the authors identified four of 10 known adenylate cyclase genes, ADCY3, ADCY6, ADCY7, and ADCY9, were enriched in their screen. Synthetic lethality with FH of these four genes, which are the most highly expressed of the 10 adenylate cyclase genes, was validated in the HEK293 cell line, a non-tumorigenic renal cell line, and the UOK262 HLRCC cell line. UOK262 cells were more sensitive to treatment with the pharmacologic adenylate cyclase inhibitor MDL-13,220A, than UOK262 cells with FH re-expressed. Synthetic lethality with the cAMP signaling pathway in FH-deficient tumors alludes to an additional therapeutic target in HLRCC.
Characteristics and the role of purinergic receptors in pathophysiology with focus on immune response
Published in International Reviews of Immunology, 2020
Marharyta Zyma, Rafał Pawliczak
The nucleotide adenosine-5′-triphosphate (ATP) is a source of energy in cells and plays a critical role in the Krebs cycle [1]. Aside from intracellular functions, the extracellular actions of purine nucleotides were represented for the first time in cardiovascular system in 1929 [2]. They can interact with specific membrane receptors as a neuromodulators, neurotransmitters, and play an important role in pathological processes. These specific membrane receptors are called purinergic receptors [1,3,4]. In 1976, these receptors were determined for the first time by Burnstock; later, in 1978, they were divided into two types (Figure 1): P1 that possesses the ability to bind adenosine and P2, which binds ATP/ADP [5]. This classification is based on some criteria: (a) the potencies of adenosine, AMP, ADP, and ATP; (b) the action of the selective antagonists, such as caffeine and theophylline; (c) the regulation of adenylate cyclase through adenosine; (d) the regulation of synthesis of prostaglandins through ATP [6].