Characterization of a stimulatory adenosine A2a receptor in adult rat ventricular myocyte

Xu, Haineng; Stein, Barry S.; Liang, Bruce T.

doi:10.1152/ajpheart.1996.270.5.h1655

Cited by 45 publications

(65 citation statements)

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“…After isolation of myocytes for 2 h, measurement of myocyte twitch amplitude was performed with the use of an optical video system, as described previously (21,24). The myocyte was placed in a perfusion chamber at room temperature under an inverted microscope (Nikon) and perfused at a rate of 2 ml/min with a Krebs bicarbonate buffer that contained (in mM) 117 NaCl, 5 KCl, 1.2 MgSO4, 1.2 KH2PO4, 1.25 CaCl 2, 25 NaHCO3, and 11 glucose, with 1% dialyzed BSA and a gas phase of 95% O 2-5% CO2, pH 7.4.…”

Section: Methodsmentioning

confidence: 99%

Modulation of β-adrenoceptor signaling in the hearts of 4-wk simulated weightlessness rats

Yin¹,

Liu²,

Fan³

et al. 2008

Journal of Applied Physiology

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Modulation of ␤-adrenoceptor signaling in the hearts of 4-wk simulated weightlessness rats. J Appl Physiol 105: 569 -574, 2008. First published May 29, 2008 doi:10.1152/japplphysiol.01381.2007.-The modulation of ␤-adrenoceptor signaling in the hearts of hindlimb unweighting (HU) simulated weightlessness rats has not been reported. In the present study, we adopted the rat tail suspension for 4 wk to simulate weightlessness; then the effects of simulated microgravity on ␤-adrenoceptor signaling were studied. Mean arterial blood pressure (ABP), left ventricular pressure (LVP), systolic function (ϩdP/dt max), and diastolic function (ϪdP/dt max) were monitored in the course of the in vivo experiment. Single rat ventricular myocyte was obtained by the enzymatic dissociation method. Hemodynamics, myocyte contraction, and cAMP production in response to ␤-adrenoceptor stimulation with isoproterenol or adenylyl cyclase stimulation with forskolin were measured, and Gs protein was also determined. Compared with the control group, no significant changes were found in heart weight, body weight and ABP, while LVP and ϮdP/dt max were significantly reduced. The ABP decrease, LVP increase, and ϮdP/dt max in response to isoproterenol administration were significantly attenuated in the HU group. The effects of isoproterenol on electrically induced singlecell contraction and cAMP production in myocytes of ventricles in the HU rats were significantly attenuated. The biologically active isoform, Gs␣ (45 kDa) in the heart, was unchanged. Both the increased electrically induced contraction and cAMP production in response to forskolin were also significantly attenuated in the simulated weightlessness rats. Above results indicated that impaired function of adenylyl cyclase causes ␤-adrenoceptor desensitization, which may be partly responsible for the depression of cardiac function. simulated weightlessness; ␤-adrenoceptor; adenylyl cyclase; cyclic adenosine 5Ј-monophosphate

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Section: Methodsmentioning

confidence: 99%

Modulation of β-adrenoceptor signaling in the hearts of 4-wk simulated weightlessness rats

Yin¹,

Liu²,

Fan³

et al. 2008

Journal of Applied Physiology

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“…These receptors were thought to primarily exist in vascular and blood cells, where they mediated vasodilatory and anti-inflammatory actions, respectively. However, expression of mRNA encoding the A 2A AR in rat ventricular myocytes (303), together with A 2A AR agonist-me-diated changes in cAMP and contraction of chick (172) and rat myocytes (56, 239,303), support the expression of A 2A ARs on myocytes. This indirect evidence of myocardial expression is supported by a single report of immunological evidence of a canine A 2A AR-like protein in human and porcine ventricular tissue (199).…”

Section: Adenosine Receptor-mediated Cardioprotection: Which Subtypesmentioning

confidence: 99%

Acute adenosinergic cardioprotection in ischemic-reperfused hearts

Headrick

Hack

Ashton

2003

American Journal of Physiology-Heart and Circulatory Physiology

148

164

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. Acute adenosinergic cardioprotection in ischemic-reperfused hearts. Am J Physiol Heart Circ Physiol 285: H1797-H1818, 2003; 10.1152/ajpheart.00407. 2003.-Cells of the cardiovascular system generate and release purine nucleoside adenosine in increasing quantities when constituent cells are "stressed" or subjected to injurious stimuli. This increased adenosine can interact with surface receptors in myocardial, vascular, fibroblast, and inflammatory cells to modulate cellular function and phenotype. Additionally, adenosine is rapidly reincorporated back into 5Ј-AMP to maintain the adenine nucleotide pool. Via these receptor-dependent and independent (metabolic) paths, adenosine can substantially modify the acute response to ischemic insult, in addition to generating a more sustained ischemia-tolerant phenotype (preconditioning). However, the molecular basis for acute adenosinergic cardioprotection remains incompletely understood and may well differ from more widely studied preconditioning. Here we review current knowledge and some controversies regarding acute cardioprotection via adenosine and adenosine receptor activation.adenosine; adenosine receptor activation; ischemia; reperfusion injury THE HEART possesses its own intrinsic protective responses, including the adenosine receptor system, which enhance resistance to ischemic insult. An understanding of the mechanisms involved in these responses not only informs us of how the heart reacts to injurious stimuli, but may provide avenues for developing novel protective strategies applicable in the setting of ischemia-reperfusion. The purine nucleoside adenosine was attributed with cardioregulatory functions almost 75 years ago (64), and since then has emerged as a crucially important control substance in essentially every tissue of the body. In the heart adenosine not only plays a role in regulating growth and differentiation, angiogenesis, coronary blood flow, cardiac conduction and heart rate, substrate metabolism, and sensitivity to adrenergic stimulation (23,67,68,73,74,260,271,283), but may play a role as an endogenous determinant of ischemic tolerance (189,225,245,259,311,312,318). From a therapeutic viewpoint, adenosine-based therapies protect against ischemic injury in a variety of animal models (72,177,208,265,288) and in human cardiac tissue (34, 36, 37,240,296). However, much remains unclear regarding the roles and mechanisms of action of adenosine in producing acute protection against ischemia and reperfusion. Generation of Endogenous Adenosine During InsultEndogenous adenosine levels increase rapidly with ischemic insult (104,109,285,286) to mediate a retaliatory response. This protective pool of adenosine can be formed via dephosphorylation of 5Ј-AMP by intra-and extracellular 5Ј-nucleotidases and from S-adenosylhomocysteine (SAH) via SAH hydrolase. Extracellular adenosine is rapidly taken into cells via a facilitative transporter (131). Within cells it is either deaminated by adenosine deaminase or rephosphorylated to 5Ј-AMP via adenosine kinase. O...

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“…A2a and A2b adenosine receptors are both present in the coronary vasculature (Mubagwa and Flameng, 2001). Message for A2a receptor has been identified in cardiomyocytes (Xu et al, 1996). The presence of A2b receptors in cardiomyocytes has been controversial (Liang and Haltiwanger, 1995;Morrison et al, 2002;Grdeń et al, 2005;Yang et al, 2006), although we have detected A2b receptor message in both rabbit and rat ventricular myocytes (unpublished observation).…”

mentioning

confidence: 51%

A_2b adenosine receptors can change their spots

Cohen

Yang

Downey

2010

British J Pharmacology

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Recently, a central role for the A2b adenosine receptor in a variety of cardiovascular functions including inflammation, erectile function, coronary artery dilation, asthma and cardioprotection has been demonstrated. Despite this evidence, the low-affinity A2b adenosine receptor is still poorly understood. This receptor appears to be very promiscuous in its coupling. In most tissues, it couples to Gs much like its cousin, the A2a adenosine receptor, but in mast cells and now, most recently, in cardiac fibroblasts, the A2b receptor also couples to Gq. Because of its low affinity, this receptor was originally thought unlikely to play any important physiological role. But the sensitivity of A2b adenosine receptors can be greatly increased by interaction with protein kinase C (PKC) making this receptor, under various conditions, both an activator and a target of PKC. We have recently documented a third coupling involving Gi. This plasticity and versatility of A2b adenosine receptors position them as potential triggers of signalling in multiple signalling cascades in many physiological responses, making this a most interesting receptor indeed.

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Characterization of a stimulatory adenosine A2a receptor in adult rat ventricular myocyte

Cited by 45 publications

References 0 publications

Modulation of β-adrenoceptor signaling in the hearts of 4-wk simulated weightlessness rats

Modulation of β-adrenoceptor signaling in the hearts of 4-wk simulated weightlessness rats

Acute adenosinergic cardioprotection in ischemic-reperfused hearts

A_2b adenosine receptors can change their spots

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Characterization of a stimulatory adenosine A2a receptor in adult rat ventricular myocyte

Cited by 45 publications

References 0 publications

Modulation of β-adrenoceptor signaling in the hearts of 4-wk simulated weightlessness rats

Modulation of β-adrenoceptor signaling in the hearts of 4-wk simulated weightlessness rats

Acute adenosinergic cardioprotection in ischemic-reperfused hearts

A2b adenosine receptors can change their spots

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A_2b adenosine receptors can change their spots