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Advances in Pharmacology

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https://www.readbyqxmd.com/read/27451104/preface
#1
EDITORIAL
Raouf A Khalil
No abstract text is available yet for this article.
2016: Advances in Pharmacology
https://www.readbyqxmd.com/read/27451103/mechanisms-of-endothelial-dysfunction-in-hypertensive-pregnancy-and-preeclampsia
#2
J S Possomato-Vieira, R A Khalil
Preeclampsia is a pregnancy-related disorder characterized by hypertension and could lead to maternal and fetal morbidity and mortality. Although the causative factors and pathophysiological mechanisms are unclear, endothelial dysfunction is a major hallmark of preeclampsia. Clinical tests and experimental research have suggested that generalized endotheliosis in the systemic, renal, cerebral, and hepatic circulation could decrease endothelium-derived vasodilators such as nitric oxide, prostacyclin, and hyperpolarization factor and increase vasoconstrictors such as endothelin-1 and thromboxane A2, leading to increased vasoconstriction, hypertension, and other manifestation of preeclampsia...
2016: Advances in Pharmacology
https://www.readbyqxmd.com/read/27451102/estrogens-and-coronary-artery-disease-new-clinical-perspectives
#3
M R Meyer, M Barton
In premenopausal women, endogenous estrogens are associated with reduced prevalence of arterial hypertension, coronary artery disease, myocardial infarction, and stroke. Clinical trials conducted in the 1990s such as HERS, WHI, and WISDOM have shown that postmenopausal treatment with horse hormone mixtures (so-called conjugated equine estrogens) and synthetic progestins adversely affects female cardiovascular health. Our understanding of rapid (nongenomic) and chronic (genomic) estrogen signaling has since advanced considerably, including identification of a new G protein-coupled estrogen receptor (GPER), which like the "classical" receptors ERα and ERβ is highly abundant in the cardiovascular system...
2016: Advances in Pharmacology
https://www.readbyqxmd.com/read/27451101/stress-induced-premature-senescence-of-endothelial-and-endothelial-progenitor-cells
#4
M S Goligorsky, K Hirschi
This brief overview of premature senescence of dysfunctional endothelial and endothelial progenitor cells provides information on endothelial cell differentiation and specialization, their ontogeny, and controversies related to endothelial stem and progenitor cells. Stressors responsible for the dysfunction of endothelial and endothelial progenitor cells, as well as cellular mechanisms and consequences of endothelial cell dysfunction are presented. Metabolic signatures of dysfunctional endothelial cells and senescence pathways are described...
2016: Advances in Pharmacology
https://www.readbyqxmd.com/read/27451100/molecular-signaling-pathways-controlling-vascular-tube-morphogenesis-and-pericyte-induced-tube-maturation-in-3d-extracellular-matrices
#5
S L K Bowers, P R Norden, G E Davis
During capillary network formation, ECs establish interconnecting tubes with defined lumens that reside within vascular guidance tunnels (physical spaces generated during EC tubulogenesis). Pericytes are recruited to EC tubes within these tunnels and capillary basement membrane deposition occurs to facilitate tube maturation. Here, we discuss molecular mechanisms controlling EC tubulogenesis demonstrating the involvement of integrins, MT1-MMP, extracellular matrix, Cdc42, Rac1, Rac2, k-Ras, Rap1b, and key downstream effectors including Pak2, Pak4, IQGAP1, MRCKβ, and Rasip1...
2016: Advances in Pharmacology
https://www.readbyqxmd.com/read/27451099/communication-through-gap-junctions-in-the-endothelium
#6
K Schmidt, R Windler, C de Wit
A swarm of fish displays a collective behavior (swarm behavior) and moves "en masse" despite the huge number of individual animals. In analogy, organ function is supported by a huge number of cells that act in an orchestrated fashion and this applies also to vascular cells along the vessel length. It is obvious that communication is required to achieve this vital goal. Gap junctions with their modular bricks, connexins (Cxs), provide channels that interlink the cytosol of adjacent cells by a pore sealed against the extracellular space...
2016: Advances in Pharmacology
https://www.readbyqxmd.com/read/27451098/endothelium-dependent-contractions-prostacyclin-and-endothelin-1-partners-in-crime
#7
O Baretella, P M Vanhoutte
Both the lipid prostacyclin and the peptide endothelin-1 are endothelium-derived substances. Endothelin-1 is one of the most powerful endogenous vasoconstrictors, while prostacyclin is a potent antiaggregatory and vasodilator mediator upon activation of prostaglandin I2 (IP) receptors. During endothelium-dependent, prostanoid-mediated contractions/constrictions, however, prostacyclin appears to be a major endothelium-derived contracting factor (EDCF). Such cyclooxygenase-dependent responses, whether measured ex vivo or in vivo, are exacerbated by aging, obesity, diabetes, or hypertension...
2016: Advances in Pharmacology
https://www.readbyqxmd.com/read/27451097/endothelin-1-biosynthesis-signaling-and-vasoreactivity
#8
M Houde, L Desbiens, P D'Orléans-Juste
Endothelin-1 (ET-1) is an extremely potent vasoconstrictor peptide originally isolated from endothelial cells. Its synthesis, mainly regulated at the gene transcription level, involves processing of a precursor by a furin-type proprotein convertase to an inactive intermediate, big ET-1. The latter peptide can then be cleaved directly by an endothelin-converting enzyme (ECE) into ET-1 or reach the active metabolite through a two-step process involving chymase hydrolyzing big ET-1 to ET-1 (1-31), itself needing conversion to ET-1 by neprilysin (NEP) to exert physiological activity...
2016: Advances in Pharmacology
https://www.readbyqxmd.com/read/27451096/epoxyeicosatrienoic-acids-and-20-hydroxyeicosatetraenoic-acid-on-endothelial-and-vascular-function
#9
J D Imig
Endothelial and vascular smooth cells generate cytochrome P450 (CYP) arachidonic acid metabolites that can impact endothelial cell function and vascular homeostasis. The objective of this review is to focus on the physiology and pharmacology of endothelial CYP metabolites. The CYP pathway produces two types of eicosanoid products: epoxyeicosatrienoic acids (EETs), formed by CYP epoxygenases, and hydroxyeicosatetraenoic acids (HETEs), formed by CYP hydroxylases. Advances in CYP enzymes, EETs, and 20-HETE by pharmacological and genetic means have led to a more complete understanding of how these eicosanoids impact on endothelial cell function...
2016: Advances in Pharmacology
https://www.readbyqxmd.com/read/27451095/endothelial-small-and-intermediate-conductance-k-channels-and-endothelium-dependent-hyperpolarization-as-drug-targets-in-cardiovascular-disease
#10
R Köhler, A Oliván-Viguera, H Wulff
Endothelial calcium/calmodulin-gated K channels of small (KCa2.3) and intermediate conductance (KCa3.1) produce membrane hyperpolarization and endothelium-dependent hyperpolarization (EDH)-mediated vasodilation. Dysfunctions of the two channels and ensuing EDH impairments are found in several cardiovascular pathologies such as diabetes, atherosclerosis, postangioplastic neointima formation, but also inflammatory disease, cancer, and organ fibrosis. Moreover, KCa3.1 plays an important role in endothelial barrier dysfunction, edema formation in cardiac and pulmonary disease, and in ischemic stroke...
2016: Advances in Pharmacology
https://www.readbyqxmd.com/read/27451094/transcriptional-and-posttranslational-regulation-of-enos-in-the-endothelium
#11
D J R Fulton
Nitric oxide (NO) is a highly reactive free radical gas and these unique properties have been adapted for a surprising number of biological roles. In neurons, NO functions as a neurotransmitter; in immune cells, NO contributes to host defense; and in endothelial cells, NO is a major regulator of blood vessel homeostasis. In the vasculature, NO is synthesized on demand by a specific enzyme, endothelial nitric oxide synthase (eNOS) that is uniquely expressed in the endothelial cells that form the interface between the circulating blood and the various tissues of the body...
2016: Advances in Pharmacology
https://www.readbyqxmd.com/read/27451093/the-endothelium-dependent-nitric-oxide-cgmp-pathway
#12
F Z Mónica, K Bian, F Murad
Nitric oxide (NO)-cyclic 3'-5' guanosine monophosphate (cGMP) signaling plays a critical role on smooth muscle tone, platelet activity, cardiac contractility, renal function and fluid balance, and cell growth. Studies of the 1990s established endothelium dysfunction as one of the major causes of cardiovascular diseases. Therapeutic strategies that benefit NO bioavailability have been applied in clinical medicine extensively. Basic and clinical studies of cGMP regulation through activation of soluble guanylyl cyclase (sGC) or inhibition of cyclic nucleotide phosphodiesterase type 5 (PDE5) have resulted in effective therapies for pulmonary hypertension, erectile dysfunction, and more recently benign prostatic hyperplasia...
2016: Advances in Pharmacology
https://www.readbyqxmd.com/read/27288084/preface
#13
EDITORIAL
Robert Schwarcz, S J Enna
No abstract text is available yet for this article.
2016: Advances in Pharmacology
https://www.readbyqxmd.com/read/27288083/foreword
#14
EDITORIAL
S H Snyder
No abstract text is available yet for this article.
2016: Advances in Pharmacology
https://www.readbyqxmd.com/read/27288082/the-nmda-receptor-and-schizophrenia-from-pathophysiology-to-treatment
#15
D T Balu
Schizophrenia is a severe mental illness that affects almost 1% of the population worldwide. Even though the etiology of schizophrenia is uncertain, it is believed to be a neurodevelopmental disorder that results from a combination of environmental insults and genetic vulnerabilities. Over the past 20 years, there has been a confluence of evidence from many research disciplines pointing to alterations in excitatory signaling, particularly involving hypofunction of the N-methyl-d-aspartate receptor (NMDAR), as a key contributor to the schizophrenia disease process...
2016: Advances in Pharmacology
https://www.readbyqxmd.com/read/27288081/the-good-and-bad-sides-of-naag
#16
P Khacho, B Wang, R Bergeron
Why has such a small peptide been the source of controversy in neuroscience over the last 5 decades? Is N-acetyl-aspartyl-glutamate (NAAG) a neurotransmitter? Is NAAG located in neuronal tissue or in astrocytes? Is NAAG involved in neuropsychiatric and neurodegenerative disorders? Is NAAG therapeutically beneficial in the treatment of stroke or in initiating cascades of events leading to psychosis? After many years of intense research there is no clear consensus within the scientific community on how NAAG behaves in the brain...
2016: Advances in Pharmacology
https://www.readbyqxmd.com/read/27288080/ultimate-translation-developing-therapeutics-targeting-on-n-methyl-d-aspartate-receptor
#17
G E Tsai
N-Methyl-d-aspartate receptors (NMDARs) are broadly distributed in the central nervous system (CNS), where they mediate excitatory signaling. NMDAR-mediated neurotransmission (NMDARMN) is the molecular engine of learning, memory and cognition, which are the basis for high cortical function. NMDARMN is also critically involved in the development and plasticity of CNS. Due to its essential and critical role, either over- or under-activation of NMDARMN can contribute substantially to the development of CNS disorders...
2016: Advances in Pharmacology
https://www.readbyqxmd.com/read/27288079/still-naag-ing-after-all-these-years-the-continuing-pursuit-of-gcpii-inhibitors
#18
J J Vornov, K R Hollinger, P F Jackson, K M Wozniak, M H Farah, P Majer, R Rais, B S Slusher
Nearly two decades ago, Joe Coyle published a single-authored review with the provocative title, The Nagging Question of the Function of N-Acetylaspartylglutamate (Coyle, 1997). In this review, Coyle documented NAAG's localization to subpopulations of glutamatergic, cholinergic, GABAergic, and noradrenergic neurons, Ca(2+)-dependent release, mGlu3 receptor agonist and NMDA receptor antagonist activity, and cleavage by the glial enzyme glutamate carboxypeptidase II (GCPII). However, at the time of his review, NAAG's physiological function as a neurotransmitter remained elusive...
2016: Advances in Pharmacology
https://www.readbyqxmd.com/read/27288078/choline-on-the-move-perspectives-on-the-molecular-physiology-and-pharmacology-of-the-presynaptic-choline-transporter
#19
E A Ennis, R D Blakely
Genetic, biochemical, physiological, and pharmacological approaches have advanced our understanding of cholinergic biology for over 100 years. High-affinity choline uptake (HACU) was one of the last features of cholinergic signaling to be defined at a molecular level, achieved through the cloning of the choline transporter (CHT, SLC5A7). In retrospect, the molecular era of CHT studies initiated with the identification of hemicholinium-3 (HC-3), a potent, competitive CHT antagonist, though it would take another 30 years before HC-3, in radiolabeled form, was used by Joseph Coyle's laboratory to identify and monitor the dynamics of CHT proteins...
2016: Advances in Pharmacology
https://www.readbyqxmd.com/read/27288077/the-long-and-winding-road-from-the-high-affinity-choline-uptake-site-to-clinical-trials-for-malignant-brain-tumors
#20
P R Lowenstein, M G Castro
Malignant brain tumors are one of the most lethal cancers. They originate from glial cells which infiltrate throughout the brain. Current standard of care involves surgical resection, radiotherapy, and chemotherapy; median survival is currently ~14-20 months postdiagnosis. Given that the brain immune system is deficient in priming systemic immune responses to glioma antigens, we proposed to reconstitute the brain immune system to achieve immunological priming from within the brain. Two adenoviral vectors are injected into the resection cavity or remaining tumor...
2016: Advances in Pharmacology
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