ACh and adenosine activate PI3-kinase in rabbit hearts through transactivation of receptor tyrosine kinases

Krieg, Thomas; Qin, Qining; McIntosh, Elizabeth; Cohen, Michael V.; Downey, James M.

doi:10.1152/ajpheart.00474.2002

Cited by 121 publications

(94 citation statements)

References 43 publications

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“…SFKs participate in GPCR-mediated transactivation of several RTKs (Keely et al, 2000;Lee and Chao, 2001;Krieg et al, 2002;Zahradka et al, 2004). Although intermediates in the pathway, we do not know whether SFKs directly phosphorylate these receptor tyrosine kinases or if the effect is indirect.…”

Section: Discussionmentioning

confidence: 97%

Protecting Motor Neurons from Toxic Insult by Antagonism of Adenosine A2a and Trk Receptors

Mojsilovic-Petrovic¹,

Jeong²,

Crocker³

et al. 2006

J. Neurosci.

131

122

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The death of motor neurons in amyotrophic lateral sclerosis (ALS) is thought to result from the interaction of a variety of factors including excitotoxicity, accumulation of toxic proteins, and abnormal axonal transport. Previously, we found that the susceptibility of motor neurons to excitotoxic insults can be limited by inhibiting signals evoked by brain-derived neurotrophic factor (BDNF) activation of the receptor tyrosine kinase B (TrkB). Here we show that this can be achieved by direct kinase inhibition or by blockade of a transactivation pathway that uses adenosine A2a receptors and src-family kinases (SFKs). Downstream signaling cascades (such as mitogen-activated protein kinase and phosphatidylinositol-3 kinase) are inhibited by these blockers. In addition to protecting motor neurons from excitotoxic insult, these agents also prevent toxicity that follows from the expression of mutant proteins (G85R superoxide dismutase 1; G59S p150 glued ) that cause familial motor neuron disease. TrkB, adenosine A2a receptors, and SFKs associate into complexes in lipid raft and nonlipid raft membranes and the signaling from lipids rafts may be particularly important because their disruption by cholesterol depletion blocks the ability of BDNF to render motor neurons vulnerable to insult. The neuroprotective versatility of Trk antagonism suggests that it may have broad utility in the treatment of ALS patients.

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Section: Discussionmentioning

confidence: 97%

Protecting Motor Neurons from Toxic Insult by Antagonism of Adenosine A2a and Trk Receptors

Mojsilovic-Petrovic¹,

Jeong²,

Crocker³

et al. 2006

J. Neurosci.

131

122

View full text Add to dashboard Cite

show abstract

“…On the other hand, transactivation of EGFR via G q -coupled receptors would decrease chloride secretion in T84 epithelial cells as a result of activation of MAPK (19). However, the coupling to either downstream effector may not be so straightforward as the occupancy of G q -coupled receptor (e.g., acetylcholine and adenosine A 1 receptor) in rabbit hearts leads to PI3-kinase activation through EGFR transactivation (20). Finally, the coupling of adenosine receptors to MAPK has been established (36), but its potential role in modulating chloride secretion remains to be examined.…”

Section: Discussionmentioning

confidence: 99%

Luminal adenosine stimulates chloride secretion through A₁receptor in mouse jejunum

Ghanem¹,

Lövdahl²,

Daré³

et al. 2005

American Journal of Physiology-Gastrointestinal and Liver Physi

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sine is known to stimulate chloride secretion by mouse jejunum. Whereas the receptor on the basolateral side is believed to be A2B, the receptor involved in the luminal effect of adenosine has not been identified. We found that jejuna expressed mRNA for all adenosine receptor subtypes. In this study, we investigated the stimulation of chloride secretion by adenosine in jejuna derived from mice lacking the adenosine receptors of A1 (A1R) and A2A (A2AR) or control littermates. The jejunal epithelium was mounted in a Ussing chamber, and a new method on the basis of impedance analysis was used to calculate the short-circuit current (I sc) values. Chloride secretion was assessed by the I sc after inhibition of the sodium-glucose cotransporter by adding phloridzin to the apical bathing solution. The effect of apical adenosine on chloride secretion was lost in jejuna from mice lacking the A 1R. There was no difference in the response to basolaterally applied adenosine or to apical forskolin. Furthermore, in jejuna from control mice, the effect of apical adenosine was also abolished in the presence of 8-cyclopentyl-1,3-dipropylxanthine, a specific A 1R antagonist. Responses to adenosine were identical in jejuna from control and A 2AR knockout mice. This study demonstrates that A1R (and not A 2AR) mediates the enhancement of chloride secretion induced by luminal adenosine in mice jejunum. intestinal secretion; diarrhea; chloride channels ADENOSINE IS AN ENDOGENOUS nucleoside that can regulate a large number of physiological and pathophysiological processes (4, 9 -16, 18, 24, 25, 31). Adenosine is generated by hydrolysis of intra-or extracellular adenine nucleotides (11).

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“…In cardiac cells, EGFR transactivation has been linked to angiotensin (Rakesh et al, 2010), muscarinic (Krieg et al, 2002;Krieg et al, 2004;Miao et al, 2015), endothelin (Kodama et al, 2002;Chen et al, 2006), opioid (Cao et al, 2005;Cohen et al, 2007;Forster et al, 2007;Zhang et al, 2015), bradykinin (Methner et al, 2009), adrenergic (Noma et al, 2007;Grisanti et al, 2014), adenosine (Williams-Pritchard et al, 2011), and sphoingosine-1 phosphate (S1P) (Hofmann et al, 2009) GPCRs, with transactivation via angiotensin II (Ang II) perhaps the most well studied. Several Gq-linked receptors (Ang II, ET-1, -ARs) may promote cardiac hypertrophy/remodelling, whereas transactivation by adenosine, opioid, bradykinin or muscarinic receptors may be protective, enhancing cell survival.…”

Section: Mechanisms Of Egfr Transactivationmentioning

confidence: 99%

“…Krieg et al (2002) initially found that acetylcholine triggered myocardial EGFR and Akt phosphorylation in an AG1478 sensitive manner, although cardiac protection appeared insensitive to the inhibitor. However, their subsequent work showed antiinfarct effects of acetylcholine and the-opioid agonist DADLE were associated with EGFR phosphorylation, and blocked by metalloproteinase inhibition (Krieg et al, 2004).…”

Section: Role Of the Egfr In Gpcr-triggered Cardioprotectionmentioning

confidence: 99%

Transactivation of the epidermal growth factor receptor in responses to myocardial stress and cardioprotection

Reichelt

O’Brien

Thomas

et al. 2017

The International Journal of Biochemistry & Cell Biology

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ACh and adenosine activate PI3-kinase in rabbit hearts through transactivation of receptor tyrosine kinases

Abstract: adenosine activate PI3-kinase in rabbit hearts through transactivation of receptor tyrosine kinases.

Cited by 121 publications

References 43 publications

Protecting Motor Neurons from Toxic Insult by Antagonism of Adenosine A2a and Trk Receptors

Protecting Motor Neurons from Toxic Insult by Antagonism of Adenosine A2a and Trk Receptors

Luminal adenosine stimulates chloride secretion through A₁receptor in mouse jejunum

Transactivation of the epidermal growth factor receptor in responses to myocardial stress and cardioprotection

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ACh and adenosine activate PI3-kinase in rabbit hearts through transactivation of receptor tyrosine kinases

Abstract: adenosine activate PI3-kinase in rabbit hearts through transactivation of receptor tyrosine kinases.

Cited by 121 publications

References 43 publications

Protecting Motor Neurons from Toxic Insult by Antagonism of Adenosine A2a and Trk Receptors

Protecting Motor Neurons from Toxic Insult by Antagonism of Adenosine A2a and Trk Receptors

Luminal adenosine stimulates chloride secretion through A1receptor in mouse jejunum

Transactivation of the epidermal growth factor receptor in responses to myocardial stress and cardioprotection

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Luminal adenosine stimulates chloride secretion through A₁receptor in mouse jejunum