Patients with achalasia lack nitric oxide synthase in the gastro-oesophageal junction.
The abnormal function of the lower oesophageal sphincter in achalasia is likely to be due to impaired nonadrenergic, noncholinergic (NANC) inhibitory input. Since recent studies in animals suggest that nitric oxide (NO) is implicated physiologically in the inhibitory responses of the lower oesophageal sphincter, we have investigated whether the synthesis of NO is altered in the gastro-oesophageal junction of patients with achalasia. NO synthase activity was investigated in samples of tissue from the gastro-oesophageal junction obtained during surgery in eight patients with typical achalasia and six non-achalasic controls who underwent oesophagectomy for reasons other than sphincter dysfunction. The NO synthase activity was determined by the transformation of 14C-L-arginine into 14C-L-citrulline in tissue homogenates. In addition, immunohistochemical staining of the tissues was performed using a polyclonal antibody raised against a peptide sequence of rat brain NO synthase. Furthermore, the relaxant response to an exogenous NO donor (sodium nitroprusside, SNP) was measured in vitro in muscle strips obtained from two patients with achalasia and in two non-achalasic controls. NO synthase activity was detected in each of the samples obtained from six control patients (0.59 +/- 0.21 pmol mg-1 min-1; mean +/- SE). By contrast, none of the samples obtained from the eight patients with achalasia had any detectable NO synthase activity. Immunohistochemical studies confirmed the presence of NO synthase in the myenteric plexus of the gastro-oesophageal junction of control patients and its absence in achalasia. SNP relaxed muscle strips precontracted with bethanechol in both control samples and those from patients with achalasia.(ABSTRACT TRUNCATED AT 250 WORDS)
Mearin
F
F
Digestive System Research Unit, Hospital General Vall d'Hebron, Autonomous University of Barcelona, Spain.
Mourelle
M
M
Guarner
F
F
Salas
A
A
Riveros-Moreno
V
V
Moncada
S
S
Malagelada
J R
JR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000594:Amino Acid Oxidoreductases / Q000032:analysis / Q000172:deficiency*; D000595:Amino Acid Sequence; D004931:Esophageal Achalasia / Q000201:enzymology*; D004943:Esophagogastric Junction / Q000201:enzymology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D019001:Nitric Oxide Synthase; D009599:Nitroprusside / Q000494:pharmacology
D009599:Nitroprusside; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases