title: Excitatory stimulation of neurons in the arcuate nucleus initiates central CRF-dependent stimulation of colonic propulsion in rats.
abstract: It is well established that autonomic control of digestive function is modulated by central autonomic neurotransmission. In this context it has been shown that digestive function can be modulated by exogenous neuropeptides microinjected into specific brain sides. Furthermore, there is considerable evidence suggesting that neurons projecting from the arcuate nucleus (ARC) to the PVN may be the source of endogenous neuropeptide release in the PVN. Neuronal projections from the ARC have been proposed to target corticotropin-releasing factor (CRF)-positive neurons in the PVN. Exogenous CRF in the PVN has been shown to modulate digestive function like gastric acid secretion and GI motility. Recently we have demonstrated that activation of ARC neurons inhibits gastric acid secretion via central CRF receptor dependent mechanisms. This poses the question whether neuronal activation of the ARC alters digestive function beside gastric acid secretion. In the present study we investigated whether CRF pathways in the ARC-PVN axis are involved in the modulation of colonic motility. First we examined the effect of an excitatory amino acid, kainate, microinjected into the ARC on colonic motility in anesthetized rats. Colonic motility was measured with a non-absorbable radioactive marker using the geometric center method. Kainate (120 pmol/rat) bilaterally microinjected into the ARC induced a significant stimulation of colonic propulsion. To assess the contribution of hypothalamic CRF to the effects of neuronal stimulation in the ARC on colonic motility we performed consecutive bilateral microinjections of an antagonist to CRF receptors into the PVN and the excitatory amino acid kainate into the ARC. Microinjection of the non-selective CRF receptor antagonist, astressin (100 ng), into the PVN abolished the stimulatory effect of neuronal activation in the ARC by kainate on colonic motor function. The data indicate that activation of neurons in the ARC stimulates colonic motility via CRF-receptor-mediated mechanism in the PVN and underlines the important role of the ARC-PVN circuit for the integrative CNS regulation of GI function.
authors.affiliation: Department of Internal Medicine, Division Gastroenterology and Endocrinology, Philipps-Universität Marburg, Baldinger Strasse 1, 35033 Marburg, Germany. tebbe@staff.uni-marburg.de
authors.forename: Johannes J
authors.initials: JJ
authors.lastname: Tebbe
authors.forename: Ileana R
authors.initials: IR
authors.lastname: Pasat
authors.forename: Hubert
authors.initials: H
authors.lastname: Mönnikes
authors.forename: Michael
authors.initials: M
authors.lastname: Ritter
authors.forename: Peter
authors.initials: P
authors.lastname: Kobelt
authors.forename: Martin K-H
authors.initials: MK
authors.lastname: Schäfer
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000502:physiology*; D003106:Colon / Q000294:innervation / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism* / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology*; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000502:physiology; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013268:Stimulation, Chemical
chemical_list: D018690:Excitatory Amino Acid Agonists; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D018019:Receptors, Corticotropin-Releasing Hormone; C104416:astressin; D003346:Corticotropin-Releasing Hormone; D007608:Kainic Acid