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Full-Text Articles in Medicine and Health Sciences
Pharmacological Characterization Of A Novel Non-At1, Non-At2 Angiotensin Binding Site Identified As Neurolysin, Jamala D. Swindle, Kira L. Santos, Robert C. Speth
Pharmacological Characterization Of A Novel Non-At1, Non-At2 Angiotensin Binding Site Identified As Neurolysin, Jamala D. Swindle, Kira L. Santos, Robert C. Speth
HPD Articles
The discovery of a novel non-AT1, non-AT2 binding site for angiotensins in the rodent brain and testis that is unmasked by the organomercurial compound para-chloromercuribenzoic acid (PCMB) has catalyzed efforts to purify and characterize this protein. We recently reported that this protein is neurolysin and now report upon the specificity of this binding site for various neuropeptides. Competition binding assays in rat brain and testis used (125)I-Sar(1), Ile(8) angiotensin II (Ang II) as the radioligand in the presence of saturating concentrations of AT1 and AT2 receptor antagonists and 100 μM parachloromercuribenzoate. Primary screening of 36 peptides and other compounds at …
The Effects Of Para-Chloromercuribenzoic Acid And Different Oxidative And Sulfhydryl Agents On A Novel, Non-At1, Non-At2 Angiotensin Binding Site Identified As Neurolysin, Kira L. Santos, Megan A. Vento, John W. Wright, Robert C. Speth
The Effects Of Para-Chloromercuribenzoic Acid And Different Oxidative And Sulfhydryl Agents On A Novel, Non-At1, Non-At2 Angiotensin Binding Site Identified As Neurolysin, Kira L. Santos, Megan A. Vento, John W. Wright, Robert C. Speth
HPD Articles
A novel, non-AT1, non-AT2 brain binding site for angiotensin peptides that is unmasked by p-chloromercuribenzoate (PCMB) has been identified as a membrane associated variant of neurolysin. The ability of different organic and inorganic oxidative and sulfhydryl reactive agents to unmask or inhibit 125I-Sar1Ile8 angiotensin II (SI-Ang II) binding to this site was presently examined. In tissue membranes from homogenates of rat brain and testis incubated in assay buffer containing losartan (10 μM) and PD123319 (10 μM) plus 100 μM PCMB, 5 of the 39 compounds tested inhibited 125I-SI Ang II binding in brain and testis. Mersalyl acid, mercuric chloride (HgCl2) …
Pancreatic Angiotensin-Converting Enzyme 2 Improves Glycemia In Angiotensin Ii-Infused Mice, Kavaljit H. Chhabra, Huijing Xia, Kim Brint Pedersen, Robert C. Speth, Eric Lazartigues
Pancreatic Angiotensin-Converting Enzyme 2 Improves Glycemia In Angiotensin Ii-Infused Mice, Kavaljit H. Chhabra, Huijing Xia, Kim Brint Pedersen, Robert C. Speth, Eric Lazartigues
HPD Articles
An overactive renin-angiotensin system (RAS) is known to contribute to type 2 diabetes mellitus (T2DM). Although ACE2 overexpression has been shown to be protective against the overactive RAS, a role for pancreatic ACE2, particularly in the islets of Langerhans, in regulating glycemia in response to elevated angiotensin II (Ang II) levels remains to be elucidated. This study examined the role of endogenous pancreatic ACE2 and the impact of elevated Ang II levels on the enzyme's ability to alleviate hyperglycemia in an Ang II infusion mouse model. Male C57bl/6J mice were infused with Ang II or saline for a period of …
Angiotensin Type 1 Receptor Resistance To Blockade In The Opossum Proximal Tubule Cell Due To Variations In The Binding Pocket, Ravi Nistala, Bradley T. Andresen, Lakshmi Pulakat, Alex Meuth, Catherine Sinak, Chirag Mandavia, Thomas Thekkumkara, Robert C. Speth, Adam Whaley-Connell, James R. Sowers
Angiotensin Type 1 Receptor Resistance To Blockade In The Opossum Proximal Tubule Cell Due To Variations In The Binding Pocket, Ravi Nistala, Bradley T. Andresen, Lakshmi Pulakat, Alex Meuth, Catherine Sinak, Chirag Mandavia, Thomas Thekkumkara, Robert C. Speth, Adam Whaley-Connell, James R. Sowers
HPD Articles
Blockade of the angiotensin (ANG) II receptor type 1 (AT(1)R) with angiotensin receptor blockers (ARBs) is widely used in the treatment of hypertension. However, ARBs are variably effective in reducing blood pressure, likely due, in part, to polymorphisms in the ARB binding pocket of the AT(1)R. Therefore, we need a better understanding of variations/polymorphisms that alter binding of ARBs in heterogeneous patient populations. The opossum proximal tubule cell (OKP) line is commonly used in research to evaluate renal sodium handling and therefore blood pressure. Investigating this issue, we found natural sequence variations in the opossum AT(1)R paralleling those observed in …
Immunohistochemical Localization Of At1a, At1b, And At2 Angiotensin Ii Receptor Subtypes In The Rat Adrenal, Pituitary, And Brain With A Perspective Commentary, Courtney Premer, Courtney Lamondin, Ann Mitzey, Robert C. Speth, Mark S. Brownfield
Immunohistochemical Localization Of At1a, At1b, And At2 Angiotensin Ii Receptor Subtypes In The Rat Adrenal, Pituitary, And Brain With A Perspective Commentary, Courtney Premer, Courtney Lamondin, Ann Mitzey, Robert C. Speth, Mark S. Brownfield
HPD Articles
Angiotensin II increases blood pressure and stimulates thirst and sodium appetite in the brain. It also stimulates secretion of aldosterone from the adrenal zona glomerulosa and epinephrine from the adrenal medulla. The rat has 3 subtypes of angiotensin II receptors: AT1a, AT1b, and AT2. mRNAs for all three subtypes occur in the adrenal and brain. To immunohistochemically differentiate these receptor subtypes, rabbits were immunized with C-terminal fragments of these subtypes to generate receptor subtype-specific antibodies. Immunofluorescence revealed AT1a and AT2 receptors in adrenal zona glomerulosa and medulla. AT1b immunofluorescence was present in the zona glomerulosa, but not the medulla. Ultrastructural …
Brain Ras: Hypertension And Beyond, Marc De Gasparo, Robert C. Speth, Ovidiu C. Baltatu, Patrick Vanderheyden
Brain Ras: Hypertension And Beyond, Marc De Gasparo, Robert C. Speth, Ovidiu C. Baltatu, Patrick Vanderheyden
HPD Articles
No abstract provided.
Adenoviral And Adeno-Associated Viral Vectors-Mediated Neuronal Gene Transfer To Cardiovascular Control Regions Of The Rat Brain, Yanling Zhang, Yongxin Gao, Robert C. Speth, Nan Jiang, Yingying Mao, Colin Sumners, Hongwei Li
Adenoviral And Adeno-Associated Viral Vectors-Mediated Neuronal Gene Transfer To Cardiovascular Control Regions Of The Rat Brain, Yanling Zhang, Yongxin Gao, Robert C. Speth, Nan Jiang, Yingying Mao, Colin Sumners, Hongwei Li
HPD Articles
Viral vectors have been utilized extensively to introduce genetic material into the central nervous system. In order to investigate gene functions in cardiovascular control regions of rat brain, we applied WPRE (woodchuck hepatitis virus post-transcriptional regulatory element) enhanced-adenoviral (Ad) and adeno-assoicated virus (AAV) type 2 vectors to mediate neuronal gene delivery to the paraventricular nucleus of the hypothalamus, the nucleus tractus solitarius and the rostral ventrolateral medulla, three important cardiovascular control regions known to express renin-angiotensin system (RAS) genes. Ad or AAV2 harboring an enhanced green fluorescent protein (EGFP) reporter gene or the angiotensin type 2 receptor gene were microinjected …
Doctor Of Philosophy In Pharmacy 2013, Nova Southeastern University
Doctor Of Philosophy In Pharmacy 2013, Nova Southeastern University
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No abstract provided.