Nociceptin inhibits gamma-aminobutyric acidergic inputs to cardiac parasympathetic neurons in the nucleus ambiguus.
Studies have shown that nociceptin, the endogenous ligand for the opioid receptor-like receptor (ORL(1)), modulates central control of cardiovascular activity. The nucleus ambiguus, an area containing cardiac parasympathetic neurons, contains both ORL(1) receptors and neurons that contain nociceptin itself. Although previous work has shown that nociceptin acts to increase parasympathetic outflow to the heart, the mechanisms by which this is achieved are unknown. In the present study, the effects of nociceptin on spontaneous gamma-aminobutyric acidergic (GABAergic) input to cardiac parasympathetic neurons (IPSCs) was examined. At 100 microM, nociceptin inhibited both the frequency (-35.6%) and the amplitude (-49.5%) of spontaneous GABAergic IPSCs in cardiac vagal neurons. Nociceptin also caused a novel postsynaptic inhibition of the responses evoked by exogenous application of GABA. These results indicate that nociceptin acts both on neurons precedent to cardiovascular neurons to decrease the activity of GABAergic neurons that synapse upon cardiovascular neurons and directly, inhibiting the postsynaptic currents evoked by GABA. This inhibition by nociceptin would increase parasympathetic outflow to the heart, thus providing a possible mechanism for nociceptin-induced bradycardia.
Venkatesan
Priya
P
Department of Pharmacology, George Washington University, Washington, DC 20037, USA.
Wang
Jijiang
J
Evans
Cory
C
Irnaten
Mustapha
M
Mendelowitz
David
D
D000818:Animals; D017776:Autonomic Pathways / Q000187:drug effects; D001933:Brain Stem / Q000166:cytology / Q000187:drug effects*; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005456:Fluorescent Dyes; D018756:GABA Antagonists / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000294:innervation*; D007395:Interneurons / Q000187:drug effects*; D018847:Opioid Peptides / Q000494:pharmacology*; D010275:Parasympathetic Nervous System / Q000166:cytology / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D014630:Vagus Nerve / Q000166:cytology / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000502:physiology*; D000097629:Nociceptin
D005456:Fluorescent Dyes; D018756:GABA Antagonists; D018847:Opioid Peptides; D005680:gamma-Aminobutyric Acid; D000097629:Nociceptin