Area postrema lesion potentiates selective and non-selective central and peripheral CRF2 receptor agonists-, Ucn 1 and Ucn 2-induced inhibition of gastric emptying

Aims: Area postrema (AP) located on the 4th brain ventricle's surface lacks normal blood-brain barrier (Van Houten et al. 1983) acts as chemoreceptor zone and has multiple neuronal connections to the nucleus of solitary tract (NTS), a regulatory key centre of gastrointestinal (GI) motility collecting afferent fibers from the GI tract. AP has also been proven to have role in regulation of gastric and colonic functions. Central Ucn 2, a CRF2 receptor agonist inhibits gastric emptying (GE) through sympathetic pathways. Aim: To characterize the role of AP in the peripheral and central CRF2 receptor peptide agonists- (Ucn 1 and Ucn 2) induced delay of GE. Methods: AP of Sprague-Dawley rats were removed by needle aspiration under microscope 10 days before intravenous (iv) injection of Ucn 1 or Ucn 2 and intracerebroventricular (icv) injection of Ucn 2. Results: 20-min-GE of a viscous methylcellulose-phenol red meal was measured (in %). Iv Ucn 2- (*24.0±8.6% compared to control 51.7±11%) or iv Ucn 1 -induced delay of GE (*19.4±10.9%) was potentiated by an AP lesion (*3.2±3.2%). The AP lesion itself did not influence GE of the sham-operated group (48.0±8.7%). Intracerebroventricular (icv) Ucn 2-induced delay of GE (*27.4±9.7% vs. controls 52.3±13.8%) was also potentiated by an AP lesion (*2.1±1.5% vs. AP lesioned controls 50.1±7.7%). Right AP lesion was tested with microscope and impairment of NaCl-aversion test. Results are expressed as means±SE of emptied percentage of gastric lavaged content in 20min.* means P<0.05 compared to respective controls. Conclusion: AP is suggested to have a role in the regulation of gastric motility through modulation of inhibitory NTS and hypothalamic sympathetic CRF2 pathways.