A lower esophageal sphincter reflex involving substance P.
The purpose of this study was to determine the mechanism by which distal esophageal acidification increases lower esophageal sphincter (LES) pressure in the anesthetized cat. Intraluminal pressures and myoelectric activity were recorded using fixed, localized manometric catheters and serosal bipolar silver-silver chloride electrodes. The increase in LES pressure (27.1 +/- 4.9 mmHg) and spike activity (133.8 +/- 22.6 spikes/min) following distal esophageal acidification were greater than after saline (P less than 0.001). These responses were abolished by either tetrodotoxin (intravenously) or intraluminal ethyl aminobenzoate. The responses were not antagonized by bilateral cervical vagotomy or by atropine, hexamethonium, phentolamine, propranolol, diphenhydramine, cimetidine, cinanserin, naloxone, haloperidol, or proglumide. Tachyphylaxis to substance P abolished the LES pressure and spike responses to exogenous substance P and to distal esophageal acidification but had no effect on the LES responses to phenylephrine (25.0 micrograms/kg iv) or pentagastrin (0.5 microgram/kg iv). The putative substance P antagonist [D-Pro2,D-Trp7,9]substance P was a partial antagonist and a weak agonist on the LES. Large doses of [D-Pro2,D-TRP7,9]substance P (200.0 micrograms/kg iv) gave a 61.3 +/- 19.3% inhibition of the LES pressure response to acid (P less than 0.05). Intravenous tetrodotoxin partially antagonized the LES response to substance P (10.0 micrograms/kg iv). These studies suggest that the increases in LES pressure and spike activity following distal esophageal acidification occur through a spike-associated enteric neural reflex that involves substance P as a neurotransmitter.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001566:Benzocaine / Q000494:pharmacology; D002415:Cats; D004943:Esophagogastric Junction / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D006874:Hydrostatic Pressure; D012018:Reflex; D013329:Structure-Activity Relationship; D013373:Substance P / Q000037:antagonists & inhibitors / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
D013373:Substance P; D013779:Tetrodotoxin; D001566:Benzocaine