Effect of substance P on the lower esophageal sphinvter and pasophysiology of esophageal achalasia

The effect of substance P on the lower esophageal sphincter (LES) was investigated in normal dogs, dogs with experimentally-induced achalasia, normal controls and patients with achalasia. 1. Substance P caused contraction and vasoactive intestinal polypeptide (VIP) relaxation of the LES. 2. Substance P-induced, but not tetragastrin-induced, contraction of the LES in normal was inhbited by atropine. 3. substance P-induced contraction of the LES was decreased in achalasia. 4. Substance P-inhibited VIP relaxation in achalasia was less than in normal sontrols. 5. Immunohistologically, the number of substance P and VIP neurons was decreased in experimental and clinical achalasia. 6. Radioimmunoassay documented a decrease in substance P and VIP concentrations in the lower esophageal musculer layer in achalasia. This suggests that substance P receptors are present in cholinergic neurons innervating the LES and VIP receptors are present on the sphincter itself. Thus a decrease in the number of substance P neurons and VIP neurons in Auerbach's plexus could cause denervation hypersensitivity of the LES to ciculating acetylcholine, which finally results in the increased LES pressure seen in achalasis.