Met(5)-enkephalin protects isolated adult rabbit cardiomyocytes via delta-opioid receptors

In rats and rabbits, endogenous opioid peptides participate in ischemic pre conditioning. However, it is not known which endogenous opioid(s) can trigg er cardioprotection. We examined preconditioning-induced and opioid-induced limitation of cell death in isolated, calcium-tolerant, adult rabbit cardi omyocytes. Cells were subjected to simulated ischemia by pelleting and norm othermic hypoxic incubation. Preconditioning was elicited with 15 min of si mulated ischemia followed by 15 min of resuspension and reoxygenation. All cells underwent 180 min of simulated ischemia. Cell death was assessed by t rypan blue permeability. Morphine protected cells, as did preconditioning; naloxone blocked the preconditioning-induced protection. Exogenous Met(5)-e nkephalin (ME) induced protection, but exogenous beta-endorphin did not. ME -induced protection was blocked by the delta-selective antagonist naltrindo le. Additionally, two other proenkephalin products, Leu(5)-enkephalin and M et(5)-enkephalin-Arg-Phe, provided protection equipotent to ME. These data suggest that one or more proenkephalin products interact with delta-opioid receptors to endogenously trigger opioid-mediated protection.