Stimulation of neurons in rat ARC inhibits gastric acid secretion via hypothalamic CRF1/2- and NPY-Y1 receptors.
Neuropeptide Y (NPY) neuronal projections from the arcuate nucleus (ARC) have been proposed to target corticotropin-releasing factor (CRF)-positive neurons in the paraventricular nucleus (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 in the PVN and of the excitatory amino acid kainate in 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 the basal condition and during pentagastrin (16 microg/kg body wt) stimulation. Microinjection of vehicle in the PVN and kainate in the ARC decreased gastric acid secretion. Microinjection of the specific NPY-Y1 receptor antagonist BIBP-3226 (200 pmol) and the nonspecific CRF1/2 antagonist astressin (30 pmol) in 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 BIIE-0246 (120 pmol) in 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.
Tebbe
Johannes J
JJ
Division of Gastroenterology and Endocrinology, Department of Internal Medicine, Philipps Universität Marburg, 35033 Marburg, Germany. tebbe@mailer.uni-marburg.de
Mronga
Silke
S
Schäfer
Martin K-H
MK
Rüter
Jens
J
Kobelt
Peter
P
Mönnikes
Hubert
H
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology / Q000502:physiology*; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D001552:Benzazepines / Q000008:administration & dosage; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage; D005744:Gastric Acid / Q000378:metabolism*; D007608:Kainic Acid / Q000008:administration & dosage; D008297:Male; D008845:Microinjections; D009474:Neurons / Q000502:physiology; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism*; D010446:Peptide Fragments / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000099052:CRF Receptor, Type 1
C092926:BIBP 3226; D001552:Benzazepines; C101531:CRF receptor type 2; D018690:Excitatory Amino Acid Agonists; D010446:Peptide Fragments; D018019:Receptors, Corticotropin-Releasing Hormone; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; C104416:astressin; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone; D001120:Arginine; C403256:BIIE 0246; D007608:Kainic Acid