Local opiate receptors in the sinoatrial node moderate vagal bradycardia.
Met-enkephalin-arg-phe (MEAP) interrupts vagal bradycardia when infused into the systemic circulation. This study was designed to locate the opiate receptors functionally responsible for this inhibition. Previous observations suggested that the receptors were most likely located in either intracardiac parasympathetic ganglia or the pre-junctional nerve terminals innervating the sinoatrial node. In this study 10 dogs were instrumented with a microdialysis probe inserted into the sinoatrial node. The functional position of the probe was tested by briefly introducing norepinephrine into the probe producing an increase in heart rate of more than 30 beats/min. Vagal stimulations were conducted at 0.5, 1.2 and 4 Hz during vehicle infusion (saline ascorbate). Cardiovascular responses during vagal stimulation were recorded on-line. MEAP was infused directly into the sinoatrial node via the microdialysis probe. The evaluation of vagal bradycardia was repeated during the nodal application of MEAP, diprenorphine (opiate antagonist), and diprenorphine co-infused with MEAP. MEAP introduced into the sinoatrial node via the microdialysis probe reduced vagal bradycardia by more than half. Simultaneous local nodal blockade of these receptors with the opiate antagonist, diprenorphine, eliminated the effect of MEAP demonstrating the participation by opiate receptors. Systemic infusions of MEAP produced a reduction in vagal bradycardia nearly identical to that observed during nodal administration. When local nodal opiate receptors were blocked with diprenorphine, the systemic effect of MEAP was eliminated. These data lead us to suggest that the opiate receptors responsible for the inhibition of vagal bradycardia are located within the sinoatrial node with few, if any, participating extra-nodal or ganglionic receptors.
Department of Biology, University of Texas/Brownsville, Brownsville, TX 78520, USA.
M
M
Farias
K
K
Jackson
A
A
Stanfill
J L
JL
Caffrey
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001919:Bradycardia / Q000139:chemically induced / Q000378:metabolism*; D003331:Coronary Vessels / Q000033:anatomy & histology; D004174:Diprenorphine / Q000494:pharmacology; D004285:Dogs; D004558:Electric Stimulation; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors; D004745:Enkephalins / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D012849:Sinoatrial Node / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism; D013566:Sympathomimetics / Q000494:pharmacology; D014630:Vagus Nerve / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D004745:Enkephalins; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D013566:Sympathomimetics; D004174:Diprenorphine; D004744:Enkephalin, Methionine; C027511:enkephalin-Met, Arg(6)-Phe(7)-; D009638:Norepinephrine