Substance P in the Dorsal Motor Nucleus of the Vagus Evokes Gastric Motor Inhibition via Neurokinin 1 Receptor in Rat 1

ABSTRACT Many gastrointestinal stimuli result in gastric fundic relaxation. This information is integrated at the interface of vagal afferents and efferents in the dorsal vagal complex. Substance P (SP) is present in this region, and the neurokinin 1 receptor (NK 1 R) is highly expressed in preganglionic neurons of the dorsal motor nucleus of the vagus (DMN). However, its functional effects on vagal motor output to the stomach have not been investigated. Therefore, we determined the gastric motor effects of stereotaxic microinjection of SP and selective tachykinin receptor agents into the DMN of anesthetized rats. Dose-related decreases in intragastric pressure and antral motility were obtained on the microinjection of SP (135 and 405 pmol) into the DMN, without cardiovascular changes. Similar decreases in intragastric pressure were noted after the microinjection of [Sar 9 ,Met(O 2 ) 11 ]SP (NK 1 R agonist; 135 pmol) but not senktide (NK 3 R agonist; 135 pmol) or vehicle. The gastric motor inhibition evoked by SP (135 pmol) was attenuated by prior microinjection of 2-methoxy-5-tetrazol-1-yl-benzyl-(2-phenyl-piperidin-3-yl)-amine (GR203040; 1 nmol; NK 1 R antagonist). Vagotomy or hexamethonium (15 mg/kg i.v.) completely abolished the gastric relaxation evoked by SP (135 pmol) microinjected into the DMN. We conclude that SP acts on NK 1 R preganglionic cholinergic vagal neurons in the DMN, which control enteric nonadrenergic noncholinergic motor inhibition of the fundus. The potential relevance is that an antiemetic site of action of NK 1 R antagonists may be in the DMN to prevent excitation of neurons controlling fundic relaxation, which is an essential prodromal component of emesis. Many stimuli to the gastrointestinal tract result in hormonal ("endoneurocrine") or neuronal feedback to other regions of the gut, and the vagus nerve is intimately involved in conveying this information to the upper gastrointestinal tract. Integration of "long-loop" vagal afferent-efferent pathways from the gut occurs in the dorsal vagal complex of the hindbrain medulla. This complex comprises the dorsal motor nucleus of the vagus (DMN), where preganglionic motor neurons innervating the gastrointestinal tract are located, and the nucleus tractus solitarius, where primary visceral afferents terminate. Preganglionic neurons in the DMN target the stomach One candidate neurotransmitter in the dorsal vagal complex that could mediate fundic relaxation is substance P (SP). The microinjection of SP into the nucleus tractus solitarius evokes gastric relaxatio

Oxytocin and Vasopressin Involved in Restraint Water-Immersion Stress Mediated by Oxytocin Receptor and Vasopressin 1b Receptor in Rat Brain

Aims: Vasopressin (AVP) and oxytocin (OT) are considered to be related to gastric functions and the regulation of stress response. The present study was to study the role of vasopressinergic and oxytocinergic neurons during the restraint waterimmersion stress. Methods: Ten male Wistar rats were divided into two groups, control and RWIS for 1h. The brain sections were treated with a dual immunohistochemistry of Fos and oxytocin (OT) or vasopressin (AVP) or OT receptor or AVP 1b receptor (V1bR). Results: (1) Fos-immunoreactive (Fos-IR) neurons dramatically increased in the hypothalamic paraventricular nucleus (PVN), the supraoptic nucleus (SON), the neucleus of solitary tract (NTS) and motor nucleus of the vagus (DMV) in the RWIS rats; (2) OT-immunoreactive (OT-IR) neurons were mainly observed in the medial magnocellular part of the PVN and the dorsal portion of the SON, while AVP-immunoreactive (AVP-IR) neurons mainly distributed in the magnocellular part of the PVN and the ventral portion of the SON. In the RWIS rats, Fos-IR neurons were indentified in 31 % of OT-IR neurons and 40 % of AVP-IR neurons in the PVN, while in the SON it represented 28%, 53 % respectively; (3) V 1bR-IR and OTR-IR neurons occupied all portions of the NTS and DMV. In the RWIS rats, more than 10 % of OTR-IR and V1bR-IR neurons were activated in the DMV, while lower ratio in the NTS. Conclusion: RWIS activates both oxytocinergic and vasopressinergic neurons in the PVN and SON, which may project to th

Entwicklung eines Prototypen für die navigierte Echtzeit-Sonographie für den Kopf-Halsbereich

Einleitung: Das Hauptproblem bei sonographisch-gesteuerten invasiven Eingriffen ist, das sich die exakte Lagebeziehung eines im dreidimensionalen Raum befindlichen chirurgischen Instruments im zweidimensionalen Ultraschallbild nur unzureichend darstellen lässt. Wir berichten über eine neue Methode, nachfolgend als navigierte Echtzeit-Sonographie bezeichnet, die es unter Verwendung eines navigierten Schallkopfs und eines navigierten chirurgischen Instruments ermöglicht, jederzeit die genaue Position des Instruments in Beziehung zur Ultraschallebene darzustellen.Methoden: Folgende Komponenten wurden verwendet: Ultraschallgerät mit navigiertem Schallkopf, navigiertes chirurgisches Instrument, PC, Koordinatengeber. Die Entwicklung umfasste folgende Arbeitsschritte: 1. Etablierung eines Kalibrierungsverfahrens, 2. Ermittlung der Zielgenauigkeit, 3. Visualisierung und praktische Handhabung. Hierzu wurden eigens Messvorrichtungen und die entsprechende Software entwickelt. Die Anwendung wurde durch 2 Kopf-Hals-Chirugen in vitro getestet.Ergebnisse: Bei der Ermittlung der Zielgenauigkeit ergab sich ein dreidimensionaler mittlerer Fehler von 0,64 ± 0,34 mm. Bei der praktischen Anwendung zeigte sich eine gute Handhabung des Systems. Die Orientierung und die Zielannäherung des Instruments erfolgte anhand der gut verständlichen Navigationshilfen rasch und zielsicher. Schlussfolgerungen: Der Vorteil dieser Methode besteht darin, dass jederzeit die exakte Position des chirurgischen Instruments bekannt ist. Im Ultraschallbild dargestellte pathologische Veränderungen können somit, beispielsweise im Rahmen von diagnostischen oder therapeutischen Eingriffen, mit dem Instrument punktgenau angesteuert werden. Veränderungen des Situs werden unmittelbar dargestellt

Orphanin FQ/nociceptin and [Phe(1)Ψ(CH(2)-NH)Gly(2)] nociceptin(1-13)-NH(2) stimulate gastric motor function in anaesthetized rats

1. Orphanin FQ/nociceptin (OFQ/N) is a preferred endogenous ligand for the orphan opioid receptor-like-1 receptor. This peptide has been reported to increase intestinal, but not gastric, motor activity. 2. In the present study, OFQ/N (0.6–60 nmol kg(−1) i.v.) increased intragastric pressure and antral contractility and, as expected, decreased blood pressure in anaesthetized rats. 3. The gastric motor effects of OFQ/N (6 nmol kg(−1)) were not affected by inhibition of nitric oxide synthase or opioid receptor blockade. 4. OFQ/N (6 nmol kg(−1)) evoked gastric motor increases and hypotension were not affected by prior administration of its derivative [Phe(1)Ψ(CH(2)-NH)Gly(2)]nociceptin-(1-13)-NH(2) unless the pseudopepotide was administered shortly (5 min) prior to OFQ/N. This putative antagonist (6–300 nmol kg(−1)) alone increased antral motility with approximately 100 fold lower potency than OFQ/N. 5. Neither bilateral vagotomy nor spinal cord transection altered OFQ/N-evoked increases in intragastric pressure and antral contractility. 6. In conclusion, OFQ/N induces gastric motor excitation in addition to its known effects to increase intestinal motility. The gastric responses to OFQ/N are not dependent on ‘classical' opioid receptor activation or nitric oxide, similar to the case for the intestines. The primary site of action of OFQ/N on the stomach is probably via enteric nerves, since central descending vagal or sympathetic pathways are not necessary for OFQ/N to increase gastric motility. The gastric motor effects of the derivative [Phe(1)Ψ(CH(2)-NH)Gly(2)]nociceptin-(1-13)-NH(2) are similar to OFQ/N, although with lower potency. The effects of the derivative as a partial agonist or antagonist in different experimental paradigms may reflect tissue OFQ/N receptor reserve