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.


RESULTS
Microdialysis probes were placed in the sinoatrial node of mongrel dogs and perfused at 5 microL/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/microL and a half-maximal response near 0.1 nmoles/microL. 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/microL with the half-maximal response near 0.1 nmoles/microL, 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 delta opiate receptor antagonist, naltrindole. Selected mu (endomorphin, super DALDA) and kappa (dynorphin, U50488) receptor agonists and mu (CTAP) and kappa (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.
Jackson
K E
KE
Department of Integrative Physiology and Cardiovascular Research Institute, University of North Texas Health Science Center in Fort Worth, Fort Worth, Texas 76107, USA.
Farias
M
M
Stanfill
A
A
Caffrey
J L
JL
D000818:Animals; D001919:Bradycardia / Q000503:physiopathology*; D004285:Dogs; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives / Q000494:pharmacology; D004745:Enkephalins / Q000737:chemistry / Q000494:pharmacology; D017551:Microdialysis; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D011498:Protein Precursors / Q000737:chemistry / Q000494:pharmacology; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors / Q000145:classification / Q000502:physiology*; D012849:Sinoatrial Node / Q000187:drug effects / Q000502:physiology*; D013566:Sympathomimetics / Q000494:pharmacology; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*
D004745:Enkephalins; D010446:Peptide Fragments; D011498:Protein Precursors; D017465:Receptors, Opioid, delta; D013566:Sympathomimetics; C029992:proenkephalin; D004744:Enkephalin, Methionine; C027511:enkephalin-Met, Arg(6)-Phe(7)-