EFFECT OF SUBSTANCE-P ON THE LOWER ESOPHAGEAL SPHINCTER WITH SPECIAL REFERENCE TO THE PATHOPHYSIOLOGY OF ACHALASIA OF THE ESOPHAGUS

Effects of substance P on the lower esophageal sphincter (LES) were investigated in normal dogs, phenol-injected achalasia dogs, control patients and achalasia patients. 1) Substance P contracted the LES in normal dogs. 2) In contraction of the LES, atropine inhibited substance P but did not inhibit tetragastrin. 3) Contractive effect of substance P in achalasia dogs was less than in normal dogs. 4) Immunohistochemical study showed that, in normal dogs and control patinets, substance P-immunoreactive nerve cells and fibers were found in abundance in the Auerbach's plexus, but in achalasia dogs and patients, they were reduced in number. 5) Radioimmunoassay indicated that, concentrations of substance P in the lower esophageal muscular layer of achalasia dogs and patients was lower than that of normal dogs and control patients. The results suggest that substance P receptors might exsist in nerve cells in the Auerbach's plexus, which supply the LES via cholinergic nerves. Decrease of substance P-nerve cells and fibers in achalasia patients might have a relationship to the hypertensive contraction of the LES.