An enteric signal regulates putative gastrointestinal presympathetic vasomotor neurons in rats.
Ingestion of a meal results in gastrointestinal (GI) hyperemia and is associated with systemic and paracrine release of a number of peptide hormones, including cholecystokinin (CCK) and 5-hydroxytryptamine (5-HT). Systemic administration of CCK octapeptide inhibits a subset of presympathetic neurons of the rostroventrolateral medulla (RVLM) that may be responsible for driving the sympathetic vasomotor tone to the GI viscera. The aim of this study was to determine whether endogenous release of CCK and/or 5-HT also inhibits CCK-sensitive RVLM neurons. The effects of intraduodenal administration of the secretagogues sodium oleate (SO) and soybean trypsin inhibitor (SBTI) on circulating levels of CCK and 5-HT were examined. In separate experiments, the discharge rates of barosensitive, medullospinal, CCK-sensitive RVLM presympathetic vasomotor neurons were recorded after rapid intraduodenal infusion of SO-SBTI or water. Alternatively, animals were pretreated with the CCK1 receptor antagonists devazepide and lorglumide or the 5-HT3 antagonist MDL-72222 before SO-SBTI administration. Secretagogue infusion significantly increased the level of circulating CCK, but not 5-HT. SO-SBTI significantly decreased (58%) the neuronal firing rate of CCK-sensitive RVLM neurons compared with water (5%). CCK1 receptor antagonists did not reverse SO-SBTI-induced neuronal inhibition (58%), whereas the 5-HT3 antagonist significantly attenuated the effect (22%). This study demonstrates a functional relation between a subset of RVLM presympathetic vasomotor neurons and meal-related signals arising from the GI tract. It is likely that endogenously released 5-HT acts in a paracrine fashion on GI 5-HT3 receptors to initiate reflex inhibition of these neurons, resulting in GI vasodilatation by withdrawal of sympathetic tone.
Sartor
Daniela M
DM
Clinical Pharmacology and Therapeutics Unit, Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria 3084, Australia. dsartor@unimelb.edu.au
Shulkes
Arthur
A
Verberne
Anthony J M
AJ
D000818:Animals; D002766:Cholecystokinin / Q000378:metabolism*; D041981:Gastrointestinal Tract / Q000502:physiology; D007422:Intestines / Q000294:innervation* / Q000502:physiology*; D008297:Male; D009046:Motor Neurons / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013116:Spinal Cord / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology*; D014666:Vasomotor System / Q000502:physiology*
D012701:Serotonin; D002766:Cholecystokinin