Endotoxin inhibits gastric emptying in rats via a capsaicin-sensitive afferent pathway.
The effects of endotoxin on gastric emptying of a solid nutrient meal and the neural mechanisms involved in such a response were investigated in conscious rats. The intraperitoneal (i.p.) administration of E. coli endotoxin (40 microg/kg) significantly reduced the 4-h rate of gastric emptying of a standard solid nutrient meal. Ablation of primary afferent neurons by systemic administration of high doses of capsaicin (20+30+50 mg/kg s.c.) to adult rats did not modify the rate of gastric emptying in control animals but prevented the delay in gastric transit induced by endotoxin. Local application of capsaicin to the vagus nerve rather than application of capsaicin to the celiac ganglion significantly repressed endotoxin-induced delay in gastric emptying. Neither treatment modified the rate of gastric emptying in vehicle-treated animals. Blockade of CGRP receptors (CGRP 8-37, 100 microg/kg i.v.) did not alter gastric emptying in control animals but significantly prevented endotoxin-induced inhibition of gastric emptying. In contrast, a tachykinin receptor antagonist ([D-Pro2, D-Trp7.9]-substance P, 2 mg/kg i.p.) significantly reduced the rate of gastric emptying in control animals and did not modify the inhibitory effects of endotoxin. Adrenergic blockade with phentolamine (3 mg/kg i.p.) +/- propranolol (5 mg/kg i.p.) or muscarinic antagonism with atropine (0.1 mg/kg i.p.) failed to reverse the delay in gastric emptying induced by endotoxin. These observations indicate that endotoxin-induced delay in gastric emptying of a solid nutrient meal is mediated by capsaicin-sensitive afferent neurons.
Department of Pharmacology, Faculty of Medicine, University of Valencia, Spain.
S
S
Calatayud
M D
MD
Barrachina
E
E
García-Zaragozá
E
E
Quintana
J V
JV
Esplugues
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000344:Afferent Pathways / Q000187:drug effects*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D002211:Capsaicin / Q000494:pharmacology*; D004347:Drug Interactions; D005746:Gastric Emptying / Q000187:drug effects* / Q000502:physiology; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D009476:Neurons, Efferent / Q000187:drug effects / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000317:Adrenergic alpha-Antagonists; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D008070:Lipopolysaccharides; D018727:Muscarinic Antagonists; D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); D001285:Atropine; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D010646:Phentolamine