Title

Endomorphin-2 inhibits GABAergic inputs to cardiac parasympathetic neurons in the nucleus ambiguus

Document Type

Journal Article

Publication Date

9-10-2002

Journal

Neuroscience

Volume

113

Issue

4

DOI

10.1016/S0306-4522(02)00244-0

Keywords

Endomorphin; Heart rate; Opiate; Opioid; Vagal

Abstract

The nucleus ambiguus is an area containing cardiac vagal neurons, from which originates most of the parasympathetic control regulating heart rate and cardiac function. GABAergic pathways to these neurons have recently been described, yet modulation of this GABAergic input and its impact upon cardiac vagal neurons is unknown. The nucleus ambiguus has been shown to contain μ-opioid receptors and endomorphin-1 and endomorphin-2, the endogenous peptide ligands for the μ-receptor, whilst microinjections of opioids in the ambiguus area evoke bradycardia. The present study therefore examined the effects of endomorphin-1, endomorphin-2 and DAMGO (a synthetic, μ-selective agonist) on spontaneous GABAergic IPSCs in cardiac parasympathetic neurons. Only endomorphin-2 (100 μM) produced a significant inhibition, of both the frequency (-22.8%) and the amplitude (-30.5%) of the spontaneous IPSCs in cardiac vagal neurons. The inhibitory effects of endomorphin-2 were blocked by naloxonazine (10 μM), a selective μ1 receptor antagonist. Naloxonazine alone (10 μM) had a potentiating effect on the frequency of the GABAergic IPSCs (+161.43%) but not on the amplitude, indicating that GABA release to cardiac vagal neurons may be under tonic control of opioids acting at the μ1 receptor. Endomorphin-2 did not reduce the responses evoked by exogenous application of GABA. These results indicate that endomorphin-2 acts on μ1 receptors located on precedent neurons to decrease GABAergic input to cardiac vagal neurons located in the nucleus ambiguus. The subsequent increase in parasympathetic outflow to the heart may be one mechanism by which μ-selective opioids act to induce bradycardia. © 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved.

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