μ-Opioid receptor stimulation in the medial subnucleus of the tractus solitarius inhibits gastric tone and motility by reducing local GABA activity

التفاصيل البيبلوغرافية
العنوان: μ-Opioid receptor stimulation in the medial subnucleus of the tractus solitarius inhibits gastric tone and motility by reducing local GABA activity
المؤلفون: Melissa A. Herman, Alisa Alayan, Richard A. Gillis, Niaz Sahibzada, Kenneth L. Dretchen, Barbara M. Bayer, Joseph G. Verbalis
المصدر: American Journal of Physiology-Gastrointestinal and Liver Physiology. 299:G494-G506
بيانات النشر: American Physiological Society, 2010.
سنة النشر: 2010
مصطلحات موضوعية: Male, medicine.medical_specialty, Microinjections, Physiology, medicine.drug_class, Narcotic Antagonists, Down-Regulation, Stimulation, Efferent Pathways, gamma-Aminobutyric acid, Neuroregulation and Motility, GABA Antagonists, Rats, Sprague-Dawley, chemistry.chemical_compound, Opioid receptor, Physiology (medical), Internal medicine, Solitary Nucleus, medicine, Animals, GABA-A Receptor Antagonists, Gastric Fundus, Opioid peptide, Neurotransmitter, gamma-Aminobutyric Acid, Neurotransmitter Agents, Hepatology, Chemistry, Solitary nucleus, Stomach, Gastroenterology, Vagus Nerve, Enkephalin, Ala(2)-MePhe(4)-Gly(5), GABA receptor antagonist, Receptors, GABA-A, Naltrexone, Rats, Vagus nerve, Endocrinology, nervous system, Muscle Tonus, Receptors, Opioid, Gastrointestinal Motility, Oligopeptides, medicine.drug
الوصف: We examined the effects of altering μ-opioid receptor (MOR) activity in the medial subnucleus of the tractus solitarius (mNTS) on several gastric end points including intragastric pressure (IGP), fundus tone, and the receptive relaxation reflex (RRR). Microinjection of the MOR agonist [d-Ala2,MePhe4,Gly(ol)5]enkephalin (DAMGO; 1–10 fmol) into the mNTS produced dose-dependent decreases in IGP. Microinjection of the endogenous MOR agonists endomorphin-1 and endomorphin-2 (20 fmol) into the mNTS mimicked the effects of 10 fmol DAMGO. Microinjection of 1 and 100 pmol DAMGO into the mNTS produced a triphasic response consisting of an initial decrease, a transient increase, and a persistent decrease in IGP. The increase in IGP appeared to be due to diffusion to the dorsal motor nucleus of the vagus. The effects of 10 fmol DAMGO in the mNTS were blocked by vagotomy and by blockade of MORs, GABAAreceptors, and ionotropic glutamate receptors in the mNTS. The RRR response was abolished by bilateral microinjection of the opioid receptor antagonist naltrexone into the mNTS and reduced by intravenous administration of naltrexone. Our data demonstrate that 1) activation of MORs in the mNTS with femtomole doses of agonist inhibits gastric motility, 2) the mechanism of MOR effects in the mNTS is through suppression of local GABA activity, and 3) blockade of MORs in the mNTS prevents the RRR response. These data suggest that opioids play an important role in mediating a vagovagal reflex through release of an endogenous opioid in the mNTS, which, in turn, inhibits ongoing local GABA activity and allows vagal sensory input to excite second-order mNTS neurons.
تدمد: 1522-1547
0193-1857
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::35c2e9c99c11ed7b69c31da48a015219
https://doi.org/10.1152/ajpgi.00038.2010
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....35c2e9c99c11ed7b69c31da48a015219
قاعدة البيانات: OpenAIRE