title: Modulation of synaptic transmission in the rat nucleus of the solitary tract by endomorphin-1.
abstract: Activation of opioid receptors in the periphery and centrally in the brain results in inhibition of gastric and other vagally mediated functions. The aim of this study was to examine the role of the endogenous opioid agonist endomorphin 1 (EM-1) in regulating synaptic transmission within the nucleus tractus solitarius (NTS), an integration site for autonomic functions. We performed whole cell patch-clamp recordings from coronal brain slices of the rat medulla. A subset of the neurons studied was prelabeled with a stomach injection of the transsynaptic retrograde virus expressing EGFP, PRV-152. Solitary tract stimulation resulted in constant latency excitatory postsynaptic currents (EPSCs) that were decreased in amplitude by EM-1 (0.01-10 microM). The paired-pulse ratio was increased with little change in input resistance, suggesting a presynaptic mechanism. Spontaneous EPSCs were decreased in both frequency and amplitude by EM-1, and miniature EPSCs were reduced in frequency but not amplitude, suggesting a presynaptic mechanism for the effect. Spontaneous inhibitory postsynaptic currents (IPSCs) were also reduced in frequency by EM-1, but the effect was blocked by TTX, suggesting activity at receptors on the somata of local inhibitory neurons. Synaptic input arising from local NTS neurons, which were activated by focal photolysis of caged glutamate, was inhibited by EM-1. The actions of EM-1 were similar to those of D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO) and were blocked by naltrexone, D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), or D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP). These results suggest that EM-1 acts at mu-opioid receptors to modulate viscerosensory input and specific components of local synaptic circuitry in the NTS.
authors.affiliation: Department of Cell and Molecular Biology, Tulane Univ., 6400 Freret St., New Orleans, LA 70118, USA.
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Glatzer
authors.forename: Bret N
authors.initials: BN
authors.lastname: Smith
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000704:Analysis of Variance; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D005971:Glutamates / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D011558:Herpesvirus 1, Suid / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009271:Naltrexone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009474:Neurons / Q000187:drug effects* / Q000821:virology; D009842:Oligopeptides / Q000494:pharmacology*; D018408:Patch-Clamp Techniques / Q000379:methods; D010446:Peptide Fragments; D010455:Peptides / Q000494:pharmacology; D010782:Photolysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017552:Solitary Nucleus / Q000166:cytology* / Q000187:drug effects / Q000821:virology; D013004:Somatostatin; D009435:Synaptic Transmission / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
chemical_list: C102508:(carboxy-2-nitrobenzyl)glutamic acid; D000701:Analgesics, Opioid; D000779:Anesthetics, Local; C529311:CTAP octapeptide; D005971:Glutamates; D009292:Narcotic Antagonists; D009842:Oligopeptides; D010446:Peptide Fragments; D010455:Peptides; C105293:endomorphin 1; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D049452:Green Fluorescent Proteins; D013779:Tetrodotoxin; D013004:Somatostatin; D009271:Naltrexone