Delta Opioid Receptors Inhibit Vagal Bradycardia in the Sinoatrial Node

Background: Methionine-enkephalin-arginine-phenylalanine (MEAP) is an endogenous opiate derived from the C-terminal sequence of the larger precursor molecule proenkephalin. This heptapeptide is abundant in the myocardium and has significant vagolytic activity when infused systemically. MEAP interrupted vagal bradycardia when it was delivered directly into the sinoatrial node by local microdialysis. This study was conducted to determine the opioid receptor responsible for the vagolytic effect of MEAP. Methods and Results: Microdialysis probes were placed in the sinoatrial node of mongrel dogs and perfused at 5 μL/min. Increasing doses of MEAP were included in the nodal perfusate and approximately two thirds of the vagal bradycardia was inhibited with a maximal effect at 0.3 nmoles/μ,L and a half-maximal response near 0.1 nmoles/,uL. When deltorphin II (a delta opioid receptor agonist) was infused into the sinoatrial node, more than 95% of the vagal bradycardia was eliminated at 0.3 nmoles/,uL with the half-maximal response near 0.1 nmoles/,L, indicating that deltorphin II was more efficacious than MEAP. The maximal deltorphin II and MEAP effects were both similarly reversed by the paired infusion of increasing doses of the 6 opiate receptor antagonist, naltrindole. Selected, μ (endomorphin, super DALDA) and κ (dynorphin, U50488) receptor agonists and,μ (CTAP) and κ (norBNI) receptor antagonists were completely ineffective in this system. Conclusions: These data suggest that the vagolytic effect of MEAP involves the activation of delta opiate receptors within the sinoatrial node.