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Full-Text Articles in Pharmacy and Pharmaceutical Sciences

Acute Repeated Intracerebroventricular Injections Of Angiotensin Ii Reduce Agonist And Antagonist Radioligand Binding In The Paraventricular Nucleus Of The Hypothalamus And Median Preoptic Nucleus In The Rat Brain, Robert C. Speth, Peter J. Vento, Eduardo J. Carrera, Luz Gonzalez-Reily, Andrea Linares, Kira Santos, Jamala D. Swindle, Derek Daniels Oct 2014

Acute Repeated Intracerebroventricular Injections Of Angiotensin Ii Reduce Agonist And Antagonist Radioligand Binding In The Paraventricular Nucleus Of The Hypothalamus And Median Preoptic Nucleus In The Rat Brain, Robert C. Speth, Peter J. Vento, Eduardo J. Carrera, Luz Gonzalez-Reily, Andrea Linares, Kira Santos, Jamala D. Swindle, Derek Daniels

HPD Articles

Angiotensin II (Ang II) stimulates water and saline intakes when injected into the brain of rats. This arises from activation of the AT1 Ang II receptor subtype. Acute repeated injections, however, decrease the water intake response to Ang II without affecting saline intake. Previous studies provide evidence that Ang II-induced water intake is mediated via the classical G protein coupling pathway, whereas the saline intake caused by Ang II is mediated by an ERK 1/2 MAP kinase signaling pathway. Accordingly, the different behavioral response to repeated injections of Ang II may reflect a selective effect on G protein coupling. To …


Increased Expression Of Angiotensin Ii Type 2 Receptors In The Solitary-Vagal Complex Blunts Renovascular Hypertension, Graziela Torres Blanch, André Henrique Freiria-Oliveira, Guilherme Fleury Speretta, Eduardo J. Carrera, Hongwei Li, Robert C. Speth, Eduardo Colombari, Colin Sumners, Débora S. Colombari Oct 2014

Increased Expression Of Angiotensin Ii Type 2 Receptors In The Solitary-Vagal Complex Blunts Renovascular Hypertension, Graziela Torres Blanch, André Henrique Freiria-Oliveira, Guilherme Fleury Speretta, Eduardo J. Carrera, Hongwei Li, Robert C. Speth, Eduardo Colombari, Colin Sumners, Débora S. Colombari

HPD Articles

Angiotensin II increases and decreases arterial pressure by acting at angiotensin type 1 and type 2 receptors, respectively. Renovascular hypertensive rats exhibit a high level of activity of the peripheral and central renin-angiotensin system. Therefore, in the present study, we evaluated the effect of increasing the expression of angiotensin type 2 receptors in the solitary-vagal complex (nucleus of the solitary tract/dorsal motor nucleus of the vagus), a key brain stem region for cardiovascular regulation, on the development of renovascular hypertension. Holtzman normotensive rats were implanted with a silver clip around the left renal artery to induce 2-kidney 1-clip renovascular hypertension. …


Selective Inhibition Of Angiotensin Receptor Signaling Through Erk1/2 Pathway By A Novel Peptide, Jun Liu, Gina L. Yosten, Hong Ji, Dan Zhang, Wei Zheng, Robert C. Speth, Willis K. Samson, Kathryn Sandberg Apr 2014

Selective Inhibition Of Angiotensin Receptor Signaling Through Erk1/2 Pathway By A Novel Peptide, Jun Liu, Gina L. Yosten, Hong Ji, Dan Zhang, Wei Zheng, Robert C. Speth, Willis K. Samson, Kathryn Sandberg

HPD Articles

A seven-amino acid peptide (PEP7) is encoded within a short open reading frame within exon 2 (E2) in the 5'-leader sequence (5'LS) upstream of the rat ANG 1a-receptor (rAT1aR) mRNA. A chemically synthesized PEP7 markedly inhibited ANG II-induced Erk1/2 activation in cell culture by 62% compared with a scrambled PEP7 (sPEP7) [pErk1/2/Erk1/2 (AU): ANG II, 1.000 ± 0.0, ANG II+PEP7, 0.3812 ± 0.086, ANG II+sPEP7, 1.069 ± 0.18; n = 3]. Under these same conditions, PEP7 had no effect on ANG II-stimulated inositol-trisphosphate production. PEP7 also had no effect on epidermal growth factor- and phorbol methyl ester-induced Erk1/2 activation, suggesting …


The Fda Funding Crisis, Judith Alphonse, Sireesha Bellam, Marlene Fernandez, Anishka Gilbert, Lauren Roper, Antonia Zapantis, Robert C. Speth Apr 2014

The Fda Funding Crisis, Judith Alphonse, Sireesha Bellam, Marlene Fernandez, Anishka Gilbert, Lauren Roper, Antonia Zapantis, Robert C. Speth

HPD Articles

The role of the Food and Drug Administration (FDA) is to ensure the safety of prescription and nonprescription drugs, dietary supplements, and the food supply, representing more than 20% of US consumer spending. The increased need to monitor imported drugs, drug products and foods, drug shortages, and compounding pharmacies bring the adequacy of FDA funding into question. Performing even at status quo cannot be accomplished if responsibilities increase without equitable funding increases: both from the federal government and fees imposed on FDA-regulated industries. Additionally, scientific advancement, new legislation, and new industries are continually increasing the FDA workload, necessitating commensurate budget …


Distribution Of Non-At1, Non-At2 Binding Of 125i-Sarcosine1, Isoleucine8 Angiotensin Ii In Neurolysin Knockout Mouse Brains, Robert C. Speth, Eduardo J. Carrera, Catalina Bretón, Andrea Linares, Luz Gonzalez-Reiley, Jamala D. Swindle, Kira L. Santos, Ines Schadock, Michael Bader, Vardan T. Karamyan Jan 2014

Distribution Of Non-At1, Non-At2 Binding Of 125i-Sarcosine1, Isoleucine8 Angiotensin Ii In Neurolysin Knockout Mouse Brains, Robert C. Speth, Eduardo J. Carrera, Catalina Bretón, Andrea Linares, Luz Gonzalez-Reiley, Jamala D. Swindle, Kira L. Santos, Ines Schadock, Michael Bader, Vardan T. Karamyan

HPD Articles

The recent identification of a novel binding site for angiotensin (Ang) II as the peptidase neurolysin (E.C. 3.4.24.16) has implications for the renin-angiotensin system (RAS). This report describes the distribution of specific binding of 125I-Sarcosine1, Isoleucine8 Ang II (125I-SI Ang II) in neurolysin knockout mouse brains compared to wild-type mouse brains using quantitative receptor autoradiography. In the presence of p-chloromercuribenzoic acid (PCMB), which unmasks the novel binding site, widespread distribution of specific (3 µM Ang II displaceable) 125I-SI Ang II binding in 32 mouse brain regions was observed. Highest levels of binding >700 fmol/g initial wet weight were seen in …


Atypical Signaling And Functional Desensitization Response Of Mas Receptor To Peptide Ligands, Kalyan C. Tirupula, Russell Desnoyer, Robert C. Speth, Sadashiva S. Karnik Jan 2014

Atypical Signaling And Functional Desensitization Response Of Mas Receptor To Peptide Ligands, Kalyan C. Tirupula, Russell Desnoyer, Robert C. Speth, Sadashiva S. Karnik

HPD Articles

MAS is a G protein-coupled receptor (GPCR) implicated in multiple physiological processes. Several physiological peptide ligands such as angiotensin-(1-7), angiotensin fragments and neuropeptide FF (NPFF) are reported to act on MAS. Studies of conventional G protein signaling and receptor desensitization upon stimulation of MAS with the peptide ligands are limited so far. Therefore, we systematically analyzed G protein signals activated by the peptide ligands. MAS-selective non-peptide ligands that were previously shown to activate G proteins were used as controls for comparison on a common cell based assay platform. Activation of MAS by the non-peptide agonist (1) increased intracellular calcium and …