This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jackson, K. E. Articles by Caffrey, J. L. Search for Related Content PubMed PubMed Citation Articles by Jackson, K. E. Articles by Caffrey, J. L. Social Bookmarking                   What's this?

Delta Opioid Receptors Inhibit Vagal Bradycardia in the Sinoatrial Node

Martin Farias

Amber Stanfill

James L. Caffrey

Department of Integrative Physiology and Cardiovascular Research Institute, University of North Texas Health Science Center in Fort Worth, Fort Worth, Texas 76107

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 (dynorphin, U50488) receptor agonists and,µ (CTAP) and (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.

Key Words: heart rate • microdialysis • enkephalin MEAP • anticholinergic

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. H. Deo, S. Johnson-Davis, M. A. Barlow, D. Yoshishige, and J. L. Caffrey Repeated {delta}1-opioid receptor stimulation reduces {delta}2-opioid receptor responses in the SA node Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2246 - H2254. [Abstract] [Full Text] [PDF]

				S. Davis, S. H. Deo, M. Barlow, D. Yoshishige, M. Farias, and J. L. Caffrey The monosialosyl ganglioside GM-1 reduces the vagolytic efficacy of {delta}2-opioid receptor stimulation Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2318 - H2326. [Abstract] [Full Text] [PDF]

				M. A. Barlow, S. Deo, S. Johnson, and J. L. Caffrey Vagotonic effects of enkephalin are not mediated by sympatholytic mechanisms. Experimental Biology and Medicine, April 1, 2006; 231(4): 387 - 395. [Abstract] [Full Text] [PDF]

				S. Pepe, O. W.V van den Brink, E. G Lakatta, and R.-P. Xiao Cross-talk of opioid peptide receptor and {beta}-adrenergic receptor signalling in the heart Cardiovasc Res, August 15, 2004; 63(3): 414 - 422. [Abstract] [Full Text] [PDF]

				M. Farias III, K. Jackson, M. Johnson, and J. L. Caffrey Cardiac enkephalins attenuate vagal bradycardia: interactions with NOS-1-cGMP systems in canine sinoatrial node Am J Physiol Heart Circ Physiol, November 1, 2003; 285(5): H2001 - H2012. [Abstract] [Full Text] [PDF]

				A. A. Stanfill, K. Jackson, M. Farias, M. Barlow, S. Deo, S. Johnson, and J. L. Caffrey Leucine-Enkephalin Interrupts Sympathetically Mediated Tachycardia Prejunctionally in the Canine Sinoatrial Node Experimental Biology and Medicine, September 1, 2003; 228(8): 898 - 906. [Abstract] [Full Text] [PDF]

				M. F. K. Jackson, D. Yoshishige, and J. L. Caffrey Bimodal {delta}-opioid receptors regulate vagal bradycardia in canine sinoatrial node Am J Physiol Heart Circ Physiol, August 7, 2003; 285(3): H1332 - H1339. [Abstract] [Full Text] [PDF]

				M. Farias III, K. E. Jackson, D. Yoshishige, and J. L. Caffrey Cardiac enkephalins interrupt vagal bradycardia via delta 2-opioid receptors in sinoatrial node Am J Physiol Heart Circ Physiol, May 1, 2003; 284(5): H1693 - H1701. [Abstract] [Full Text] [PDF]