TAN-67, a delta 1-opioid receptor agonist, reduces infarct size via activation of Gi/o proteins and KATP channels

The American Journal of Physiology
Schultz J el-JG J Gross

Abstract

We have previously shown that delta (delta)-opioid receptors, most notably delta 1, are involved in the cardioprotective effect of ischemic preconditioning (PC) in rats; however, the mechanism by which delta-opioid receptor-induced cardioprotection is mediated remains unknown. Therefore, we hypothesized that several of the known mediators of ischemic PC such as the ATP-sensitive potassium (KATP) channel and Gi/o proteins are involved in the cardioprotective effect produced by delta 1-opioid receptor activation. To address these possibilities, anesthetized, open-chest Wistar rats were randomly assigned to five groups. Control animals were subjected to 30 min of coronary artery occlusion and 2 h of reperfusion. To demonstrate that stimulating delta 1-opioid receptors produces cardioprotection, TAN-67, a new selective delta 1-agonist, was infused for 15 min before the long occlusion and reperfusion periods. In addition, one group received 7-benzylidenenaltrexone (BNTX), a selective delta 1-antagonist, before TAN-67. To study the involvement of KATP channels or Gi/o proteins in delta 1-opioid receptor-induced cardioprotection, glibenclamide (Glib), a KATP channel antagonist, or pertussis toxin (PTX), an inhibitor of Gi/o proteins, ...Continue Reading

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