Submitted on March 18, 2003
Accepted on June 30, 2003
Stimulation of neurons in the arcuate nucleus inhibits gastric acid secretion via hypothalamic CRF-1/2- and NPY-Y1-receptors in rats: Evidence of central autonomic control of gastrointestinal function by the arcuato-paraventricular neuronal system (ARC-PVN axis)
Johannes J. Tebbe1*, Silke Mronga1, Martin K. -H. Schafer2, Jens Ruter3, Peter Kobelt3, and Hubert Monnikes3
1 Department of Internal Medicine , Division Gastroenterology and Endocrinology, Philipps Universitat, Marburg, Germany
2 Institute of Anatomy and Cell Biology, Department of Molecular Neuroscience, Phillipps Universitat, Marburg, Germany
3 Department of Medicine, Division Hepatology and Gastroenterology and Division Psychosomatics and Psychotherapy, Humboldt Universitat, Charite - Campus Virchow-Klinikum, Berlin, Germany
* To whom correspondence should be addressed. E-mail: tebbe{at}mailer.uni-marburg.de.
Neuropeptide Y (NPY) neuronal projections from the ARC have been proposed to target corticotropin-releasing factor (CRF)-positive neurons in the PVN as part of the ARC-PVN axis. The existence of a positive feedback loop involving CRF-receptors in the PVN has been suggested. Exogenous NPY and CRF in the PVN have been shown to inhibit gastric acid secretion. Recently we have demonstrated that activation of ARC neurons inhibits gastric acid secretion via vagal pathways. To what extent NPY- and CRF-mediated mechanisms in the PVN contribute to the CNS modulation of gastric acid secretion is still an open question.
In the present study we performed consecutive bilateral microinjections of antagonists to NPY receptor subtypes Y1 and Y2 and to CRF1/2 receptors into the PVN and of the excitatory amino acid kainate into the ARC to assess the role of NPY- and CRF-mediated mechanisms in the kainate induced effects on gastric acid secretion. Gastric acid secretion was measured at basal condition and pentagastrin (16 µg/kg/BW) stimulation. Microinjection of vehicle into the PVN and kainate into the ARC decreased gastric acid secretion. Microinjection of the specific NPY-Y1-receptor antagonist BIBP3226 (200 pmol) and the non-specific CRF1/2-antagonist astressin (30 pmol) into the PVN abolished the inhibitory effect of neuronal activation in the ARC by kainate on gastric acid secretion. The CRF-antagonist astressin was more effective. Pretreatment with the NPY-Y2-receptor antagonist BIIE0246 (120 pmol) into the PVN had no significant effect. Our results indicate that activation of neurons in the ARC inhibits gastric acid secretion via CRF1/2- and NPY-Y1-receptor mediated pathways in the PVN.
