10 results match your criteria a61603 stimulated

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Coupling to Gq Signaling Is Required for Cardioprotection by an Alpha-1A-Adrenergic Receptor Agonist.

Circ Res 2019 09 20;125(7):699-706. Epub 2019 Aug 20.

From the VA Medical Center, San Francisco, CA (B.-E.M., P.M.S., A.R., A.J.B., P.C.S.).

Rationale: Gq signaling in cardiac myocytes is classically considered toxic. Targeting Gq directly to test this is problematic, because cardiac myocytes have many Gq-coupled receptors.

Objective: Test whether Gq coupling is required for the cardioprotective effects of an alpha-1A-AR (adrenergic receptor) agonist. Read More

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September 2019

Calcium/calmodulin regulates signaling at the α adrenoceptor.

Eur J Pharmacol 2019 Apr 25;848:70-79. Epub 2019 Jan 25.

Department of Physiology and Pharmacology, Des Moines University Osteopathic Medical Center, Ryan Hall 258, 3200 Grand Avenue, Des Moines, IA 50312, United States. Electronic address:

Cardiovascular functions are mediated by multiple 7-pass transmembrane receptors whose activation promotes contraction or relaxation of the tissues. The α adrenoceptor type 1A plays important roles in the control of vascular tone and myocardial contractility via Ca-dependent actions. Here, using novel FRET-based biosensors, we identified a novel Ca-dependent interaction between calmodulin (CaM) and the human α adrenoceptor at the juxtamembranous region of its 4th submembrane domain (SMD4, a. Read More

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α-Adrenoceptors activate mTOR signalling and glucose uptake in cardiomyocytes.

Biochem Pharmacol 2018 02 24;148:27-40. Epub 2017 Nov 24.

Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, SE-106 91 Stockholm, Sweden. Electronic address:

The capacity of G protein-coupled receptors to modulate mechanistic target of rapamycin (mTOR) activity is a newly emerging paradigm with the potential to link cell surface receptors with cell survival. Cardiomyocyte viability is linked to signalling pathways involving Akt and mTOR, as well as increased glucose uptake and utilization. Our aim was to determine whether the α-adrenoceptor (AR) couples to these protective pathways, and increased glucose uptake. Read More

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February 2018

A Myocardial Slice Culture Model Reveals Alpha-1A-Adrenergic Receptor Signaling in the Human Heart.

JACC Basic Transl Sci 2016 04;1(3):155-167

Department of Medicine, VA Medical Center, San Francisco, CA; Department of Medicine, University of California, San Francisco.

Background: Translation of preclinical findings could benefit from a simple, reproducible, high throughput human model to study myocardial signaling. Alpha-1A-adrenergic receptors (ARs) are expressed at very low levels in the human heart, and it is unknown if they function.

Objectives: To develop a high throughput human myocardial slice culture model, and to test the hypothesis that alpha-1A- ARs are functional in the human heart. Read More

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The Alpha-1A Adrenergic Receptor in the Rabbit Heart.

PLoS One 2016 3;11(6):e0155238. Epub 2016 Jun 3.

Department of Medicine, Cardiology Division, and Research Service, VA Medical Center, San Francisco, CA, United States of America.

The alpha-1A-adrenergic receptor (AR) subtype is associated with cardioprotective signaling in the mouse and human heart. The rabbit is useful for cardiac disease modeling, but data on the alpha-1A in the rabbit heart are limited. Our objective was to test for expression and function of the alpha-1A in rabbit heart. Read More

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The α1A-adrenergic receptor subtype mediates increased contraction of failing right ventricular myocardium.

Am J Physiol Heart Circ Physiol 2015 Sep 26;309(5):H888-96. Epub 2015 Jun 26.

Veterans Affairs Medical Center, San Francisco, and Department of Medicine, University California San Francisco, San Francisco, California; and

Dysfunction of the right ventricle (RV) is closely related to prognosis for patients with RV failure. Therefore, strategies to improve failing RV function are significant. In a mouse RV failure model, we previously reported that α1-adrenergic receptor (α1-AR) inotropic responses are increased. Read More

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September 2015

Dopamine D₁-like receptors regulate the α₁A-adrenergic receptor in human renal proximal tubule cells and D₁-like dopamine receptor knockout mice.

Am J Physiol Renal Physiol 2014 Dec 22;307(11):F1238-48. Epub 2014 Oct 22.

Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland;

The homeostatic control of blood pressure hinges upon the delicate balance between prohypertensinogenic and antihypertensinogenic systems. D₁-like dopamine receptors [dopamine D₁ and D₅ receptors (D₁Rs and D₅Rs, respectively)] and the α₁A-adrenergic receptor (α₁A-AR) are expressed in the renal proximal tubule and engender opposing effects on Na(+) transport, i.e. Read More

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December 2014

Functional alpha(1)-adrenoceptor subtypes in human submandibular glands.

J Dent Res 2006 Mar;85(3):251-6

Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Zhong Guan Cun South St. 22, 100081 Beijing, PRC.

alpha(1)-Adrenoceptor has been discovered to exist in many human tissues and mediates important physiological functions. The purpose of this study was to detect the expression, distribution, and function of alpha(1)-adrenoceptor subtypes in human submandibular glands. alpha(1A)- and alpha(1B)-Adrenoceptor mRNAs were identified by reverse-transcription/polymerase chain-reaction (RT-PCR), and their proteins were detected by Western blotting. Read More

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Regulation of alpha(1)-adrenoceptor-linked phosphoinositide metabolism in cultured glia: involvement of protein phosphatases and kinases.

Cell Signal 2003 Apr;15(4):403-12

Department of Pharmacology, The School of Pharmacy, 29/39 Brunswick Square, London WC1N 1AX, UK.

Noradrenaline-stimulated phosphoinositide breakdown in cultured glia was found to be mediated by alpha(1A)-adrenoceptors. The alpha(1A)-selective agonist A61603 was as effective as noradrenaline in eliciting 3H-inositol phosphate (IP) accumulation but was approximately 50-fold more potent. In addition, the use of selective antagonists revealed a clear rank order of potency in the ability of these drugs to reverse the effect of noradrenaline on phosphoinositide breakdown: RS17053 (alpha(1A)-selective) >>AH11110A (alpha(1B)-selective)>BMY7378 (alpha(1D)-selective). Read More

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The alpha(1)-adrenoceptor subtype- and protein kinase C isoform-dependence of Norepinephrine's actions in cardiomyocytes.

J Mol Cell Cardiol 2000 Jul;32(7):1193-209

Department of Pharmacology, Columbia University, New York, NY 10032, USA.

Catecholamines modulate cardiac function at least in part through alpha(1)-adrenergic receptors linked to the activation of protein kinase C (PKC). This study examines the molecular forms of the alpha(1)-receptor and PKC that mediate norepinephrine's actions in cardiomyocytes; distinct approaches (activation-dependent down-regulation of PKC isoforms) and novel reagents (A61603, an alpha(1A/c)-receptor agonist) are used to resolve this issue which has been the focus of dispute in previous studies. Norepinephrine (NE) induces a rise in diacylglycerol levels which is sustained for 24 h and is associated with the translocation (at 5 min) and down-regulation (at 24 h) of PKC delta and PKC xi (but not PKC alpha). Read More

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