Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0037315 (sleep apnea)
 8,000 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vasoactive intestinal polypeptide (VIP) is a neurotransmitter of the non-adrenergic and non-cholinergic system (NANC). It has been detected in many organs, including the airways, central and peripheral nervous system, the blood, and CSF. As a result of neuronal overflow, vagal stimulation leads to an elevation of VIP levels in the plasma. VIP leads to the activation of adenyl-cyclase, and thus to elevated cAMP in cells bearing VIP receptors. In 25 patients (24 males, 1 female) with a mean age of 50.3 +/- 9.9 years, and a Broca Index of 134.5 +/- 27.0%, plasma VIP was measured in the morning under conditions of fasting with the aid of an RIA assay (Incstar). Eleven patients (mean age: 49.4 +/- 10.1 years, Broca: 130 +/- 27.0%) had fewer than 100 episodes of apnea during nocturnal sleep (apnea/hypoapnea index 4.4 +/- 4.8). At 6.3 +/- 1.6 pcmoll-1, plasma VIP was markedly lower than that measured in 14 patients (mean age: 51.0 +/- 10.0 years, Broca: 138 +/- 28%) with the sleep apnea syndrome (apnea/hypopnea index 58.5 +/- 24.7 (means = 11.0 +/- 3.0 pcmoll-1, p less than 0.001). A significant correlation was found between the apnea episode occurring every night, and the VIP values (r = 0.64; y = -133 + 40 x VIP) measured in the plasma. The VIP measured in the plasma would appear to be a highly sensitive and highly specific indicator of the appearance of episodes of apnea during nocturnal sleep.
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PMID:[The significance of vasoactive intestinal polypeptide (VIP) in diagnosis of sleep apnea syndrome]. 260 48

Adenosine 3',5'-monophosphate (cyclic AMP), 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) were determined in the cerebrospinal fluid of patients with respiratory disorder and hypersomnia and in control patients. Patients with the sleep apnoea syndrome confirmed polygraphically showed elevated levels of cyclic AMP and 5-HIAA. Cyclic AMP levels were inversely correlated with arterial Po(2), measured under resting conditions. The level of HVA also was raised, but the change was not statistically significant.
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PMID:Cerebrospinal fluid adenosine 3',5'-monophosphate, 5-hydroxyindoleacetic acid and homovanillic acid in patients with sleep apnoea syndrome. 617

Protein kinase A (PKA) is a multi-unit protein kinase that mediates signal transduction of G-protein-coupled receptors through its activation by adenyl cyclase (AC)-mediated cAMP. The vital importance of PKA signaling to cellular function is reflected in the widespread expression of PKA subunit genes. As one of its many functions, PKA plays a key role in the regulation of metabolism and triglyceride storage. The PKA pathway has become of great interest to the study of aging, since mutations that cause a reduction in PKA signaling have been shown to extend lifespan in yeast, and to both delay the incidence and severity of age-related disease, and to promote leanness and longevity, in mice. There is increasing interest in the potential for the inhibition or redistribution of adiposity to attenuate aging, since obesity is associated with impaired function of most organ systems, and is a strong risk factor for shortened life span. Its association with coronary heart disease, hypertension, type 2 diabetes, cancer, sleep apnea and osteoarthritis is leading to its accession as a major cause of global ill health. Therefore, gene signaling pathways such as PKA that promote adiposity are potential inhibitory targets for aging intervention. Since numerous plant compounds have been found that both prevent adipogenesis and inhibit PKA signaling, a focused investigation into their effects on biological systems and the corresponding molecular mechanisms would be of high relevance to the discovery of novel and non-toxic compounds that promote healthy aging.
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PMID:Protein kinase A signaling as an anti-aging target. 2018 16

Intermittent hypoxia (IH) associated with sleep apnea leads to cardio-respiratory morbidities. Previous studies have shown that IH alters the synthesis of neurotransmitters including catecholamines and neuropeptides in brainstem regions associated with regulation of cardio-respiratory functions. GABA, a major inhibitory neurotransmitter in the CNS, has been implicated in cardio-respiratory control. GABA synthesis is primarily catalyzed by glutamic acid decarboxylase (GAD). In this study, we tested the hypothesis that IH like its effect on other transmitters also alters GABA synthesis. The impact of IH on GABA synthesis was investigated in pheochromocytoma 12 cells, a neuronal cell line which is known to express active form of GAD67 in the cytosolic fraction and also assessed the underlying mechanisms contributing to IH-evoked response. Exposure of cell cultures to IH decreased GAD67 activity and GABA level. IH-evoked decrease in GAD67 activity was caused by increased cAMP - protein kinase A (PKA) - dependent phosphorylation of GAD67, but not as a result of changes in either GAD67 mRNA or protein expression. PKA inhibitor restored GAD67 activity and GABA levels in IH treated cells. Pheochromocytoma 12 cells express dopamine 1 receptor (D1R), a G-protein coupled receptor whose activation increased adenylyl cyclase activity. Treatment with either D1R antagonist or adenylyl cyclase inhibitor reversed IH-evoked GAD67 inhibition. Silencing D1R expression with siRNA reversed cAMP elevation and GAD67 inhibition by IH. These results provide evidence for the role of D1R-cAMP-PKA signaling in IH-mediated inhibition of GAD67 via protein phosphorylation resulting in down-regulation of GABA synthesis.
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PMID:Post-translational modification of glutamic acid decarboxylase 67 by intermittent hypoxia: evidence for the involvement of dopamine D1 receptor signaling. 2096 67

Repetitive hypoxia is a key feature of obstructive sleep apnoea (OSA), a condition characterized by intermittent airways obstruction. Patients with OSA present with persistent increases in sympathetic activity and commonly develop hypertension. The objectives of this study were to determine if the persistent increases in sympathetic nerve activity, known to be induced by acute intermittent hypoxia (AIH), are mediated through activation of the pituitary adenylate cyclase activating polypeptide (PACAP) signaling system. Here, we show that the excitatory neuropeptide PACAP, acting in the spinal cord, is important for generating the sympathetic response seen following AIH. Using PACAP receptor knockout mice, and pharmacological agents in Sprague Dawley rats, we measured blood pressure, heart rate, pH, PaCO2, and splanchnic sympathetic nerve activity, under anaesthesia, to demonstrate that the sympathetic response to AIH is mediated via the PAC1 receptor, in a cAMP-dependent manner. We also report that both intermittent microinjection of glutamate into the rostroventrolateral medulla (RVLM) and intermittent infusion of a sub-threshold dose of PACAP into the subarachnoid space can mimic the sympathetic response to AIH. All the sympathetic responses are independent of blood pressure, pH or PaCO2 changes. Our results show that in AIH, PACAP signaling in the spinal cord helps drive persistent increases in sympathetic nerve activity. This mechanism may be a precursor to the development of hypertension in conditions of chronic intermittent hypoxia, such as OSA.
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PMID:PACAP-PAC1 Receptor Activation Is Necessary for the Sympathetic Response to Acute Intermittent Hypoxia. 3149 33