Dual activation of adenosine A1 and A3 receptors mediates preconditioning of isolated cardiac myocytes

Wang, Jianxun; Drake, Lisa A.; Sajjadi, Fereydoun G.; Firestein, Gary S.; Mullane, Kevin; Bullough, David A.

doi:10.1016/s0014-2999(96)00901-6

Cited by 59 publications

(41 citation statements)

References 33 publications

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“…Some studies have shown that activation of either A 1 or A 3 ARs could trigger protection of function in preconditioned rat hearts, although maximal preconditioning requires activation of both A 1 and A 3 ARs 85,86 . The selective agonists CCPA and Cl-IB-MECA have been used to discern two separate A 1 and A 3 AR-mediated pathways leading to cardioprotection, either as early or late preconditioning or during prolonged ischaemia.…”

Section: Ischaemiamentioning

confidence: 99%

Adenosine receptors as therapeutic targets

Jacobson

Gao

2006

Nat Rev Drug Discov

1,289

1,361

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Adenosine receptors are major targets of caffeine, the most commonly consumed drug in the world. There is growing evidence that they could also be promising therapeutic targets in a wide range of conditions, including cerebral and cardiac ischaemic diseases, sleep disorders, immune and inflammatory disorders and cancer. After more than three decades of medicinal chemistry research, a considerable number of selective agonists and antagonists of adenosine receptors have been discovered, and some have been clinically evaluated, although none has yet received regulatory approval. However, recent advances in the understanding of the roles of the various adenosine receptor subtypes, and in the development of selective and potent ligands, as discussed in this review, have brought the goal of therapeutic application of adenosine receptor modulators considerably closer.

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Section: Ischaemiamentioning

confidence: 99%

Adenosine receptors as therapeutic targets

Jacobson

Gao

2006

Nat Rev Drug Discov

1,289

1,361

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“…However, the relative contribution of A 1 AR to modulation of coronary circulation remains to be elucidated. A 1 AR have been known to protect against the injury caused by myocardial ischemia and reperfusion by inhibiting adenylyl cyclase and activating ATP-dependent potassium channels (15,16,23,36). With increasing interest in the clinical use of adenosine or A 1 AR agonists to protect ischemic myocardium (13, 14, 18 -20), it will be important to determine whether and to what extent selective manipulation (activation/antagonism) of A 1 AR might affect coronary flow.…”

mentioning

confidence: 99%

Role of A₁ adenosine receptor in the regulation of coronary flow

Tawfik¹,

Teng²,

Morrison³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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To determine whether A1 adenosine receptors (AR) participate in adenosine-induced changes of coronary flow, isolated hearts from A1AR−/− and A1AR+/+ mice were perfused under constant pressure, and the effects of nonselective and selective agonists were examined. Adenosine, 5′- N-ethylcarboxamidoadenosine (NECA, nonselective), and the selective A2AAR agonist 2–2-carboxyethylphenethylamino-5′- N-ethylcarboxamidoadenosine (CGS-21680) augmented maximal coronary vasodilation in A1AR−/− hearts compared with A1AR+/+ hearts. Basal coronary flow was increased ( P < 0.05) in A1AR−/− hearts compared with A1AR+/+ hearts: 2.548 ± 0.1 vs. 2.059 ± 0.17 ml/min. In addition, selective activation of A1AR with 2-chloro- N6-cyclopentyladenosine (CCPA) at nanomolar concentrations (1–100 nM) did not significantly change coronary flow; at higher concentrations, CCPA increased coronary flow in A1AR−/− and A1AR+/+ hearts. Because deletion of A1AR increased basal coronary flow, it is speculated that this effect is due to removal of an inhibitory influence associated with A1AR. Adenosine and NECA at approximately EC50 (100 and 50 nM, respectively) increased coronary flow in A1AR+/+ hearts to 177.86 ± 8.75 and 172.72 ± 17% of baseline, respectively. In the presence of the selective A1AR antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 50 nM), the adenosine- and NECA-induced increase in coronary flow in A1AR+/+ hearts was significantly augmented to 216.106 ± 8.35 and 201.61 ± 21.89% of normalized baseline values, respectively. The adenosine- and NECA-induced increase in coronary flow in A1AR−/− hearts was not altered by DPCPX. These data indicate that A1AR may inhibit or negatively modulate coronary flow mediated by other AR subtypes (A2A and A2B).

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“…Thus, an adenosine receptor agonist can simulate the preconditioning whereas an adenosine receptor antagonist blocks its beneficial effect. 5 Also, recent studies in cerebral ischemia, have obtained evidence that the response to adenosine persists or is enhanced by nucleoside transport inhibitors such as propentofylline. Inhibition of adenosine uptake would increase its concentration in the extracellular space and hence potentiate its effects, particularly if adenosine binds to a specific receptor site on the external surface of the membrane.…”

mentioning

confidence: 99%

“…Inhibition of adenosine uptake would increase its concentration in the extracellular space and hence potentiate its effects, particularly if adenosine binds to a specific receptor site on the external surface of the membrane. 6 Adenosine receptors have been divided into three major subclasses: A 1 , A 2 , and A 3 , 5,7 and it is known that adenosine mainly stimulates the A 1 and A 2 receptor subtypes. 8 Despite evidence in the heart that adenosine receptors could be involved in the preconditioning process, the specific contributions of individual receptor subtypes are less well defined.…”

mentioning

confidence: 99%

The Protective Role of Adenosine in Inducing Nitric Oxide Synthesis in Rat Liver Ischemia Preconditioning Is Mediated by Activation of Adenosine A2 Receptors

et al. 1999

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This study aims to determine if the protective role of adenosine in liver ischemic preconditioning is mediated by the activation of adenosine receptors and to ascertain which of these receptors is implicated in the process. Administration of adenosine A 1 and A 2 receptor antagonists to preconditioned animals indicates that hepatic preconditioning is mediated by the activation of adenosine A 2 receptors. Propentofylline (an inhibitor of adenosine transport into cells) in the preconditioned group, subjected to previous administration of an adenosine A 2 receptor antagonist, prevented the negative effect of the latter on the protection offered by preconditioning. An increase of NO production was detected just immediately after hepatic preconditioning, and the administration of an adenosine A 2 receptor antagonist to the preconditioning group prevented this increase, thus abolishing the protective effect of preconditioning. However, the administration of a NO donor to the preconditioned group subjected to previous administration of the adenosine A 2 receptor antagonist was able to maintain the preconditioning effects. In conclusion, these results indicate that, in preconditioning, the protective effect of adenosine could be a result of an increase in extracellular adenosine. This in turn would induce the activation of adenosine A 2 receptors, which, by eliciting an increase in NO generation, would protect against the injury associated with hepatic ischemia-reperfusion. (HEPATOLOGY 1999;29: 126-132.)Ischemic preconditioning, first shown in the myocardium has become a phenomenon described in the intestine, 1 brain, 2 and liver. 3 We have previously shown that ischemic preconditioning, induced by brief ischemia and reperfusion periods, renders the liver more tolerant to subsequent sustained ischemia-reperfusion. 4 We have also shown that the administration of adenosine mimics the effect of preconditioning in ischemic livers, and that the metabolization of endogenous adenosine by adenosine deaminase abolished the protective effect of preconditioning. We have further shown the beneficial effect of adenosine in inducing NO synthesis in ischemic tissue, 4 although the exact mechanism by which adenosine offered protection was not determined in that study. Recent work in heart preconditioning has shown that preconditioning-induced protection may require the activation of adenosine receptors. Thus, an adenosine receptor agonist can simulate the preconditioning whereas an adenosine receptor antagonist blocks its beneficial effect. 5 Also, recent studies in cerebral ischemia, have obtained evidence that the response to adenosine persists or is enhanced by nucleoside transport inhibitors such as propentofylline. Inhibition of adenosine uptake would increase its concentration in the extracellular space and hence potentiate its effects, particularly if adenosine binds to a specific receptor site on the external surface of the membrane. 6 Adenosine receptors have been divided into three major subclasses: A 1 , A 2 , and A 3 , 5,7 ...

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Dual activation of adenosine A1 and A3 receptors mediates preconditioning of isolated cardiac myocytes

Cited by 59 publications

References 33 publications

Adenosine receptors as therapeutic targets

Adenosine receptors as therapeutic targets

Role of A₁ adenosine receptor in the regulation of coronary flow

The Protective Role of Adenosine in Inducing Nitric Oxide Synthesis in Rat Liver Ischemia Preconditioning Is Mediated by Activation of Adenosine A2 Receptors

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Dual activation of adenosine A1 and A3 receptors mediates preconditioning of isolated cardiac myocytes

Cited by 59 publications

References 33 publications

Adenosine receptors as therapeutic targets

Adenosine receptors as therapeutic targets

Role of A1 adenosine receptor in the regulation of coronary flow

The Protective Role of Adenosine in Inducing Nitric Oxide Synthesis in Rat Liver Ischemia Preconditioning Is Mediated by Activation of Adenosine A2 Receptors

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Role of A₁ adenosine receptor in the regulation of coronary flow