Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0014848 (achalasia)
 2,804 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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)
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PMID:Patients with achalasia lack nitric oxide synthase in the gastro-oesophageal junction. 750 98

Nitric oxide (NO) is a neurotransmitter and neuromodulator in the central nervous system, but this small labile substance also seems to serve as a peripheral neurotransmitter. Abundant evidence is now available that NO, synthesized from L-arginine by NO synthase (NOS), is a nonadrenergic noncholinergic relaxant transmitter of gastrointestinal smooth muscle. Electrically induced nonadrenergic noncholinergic relaxations are antagonized by NOS inhibitors in vitro and in vivo. In a bioassay superfusion system, the release of a substance with the pharmacological characteristics of NO from a gastrointestinal smooth muscle preparation was detected; also, indirect measurements (e.g. of the NO metabolite nitrite or of the co-product of its synthesis L-citrulline) suggest NO release. Immunohistochemistry with antibodies raised against the neuronal NOS showed immunoreactivity in cell bodies of neurones in the myenteric plexus and in nerve fibres in the muscular layer. These data suggest that nerve endings, innervating smooth muscle, are able to release NO that will penetrate the cells to induce relaxation (i.e. nitrergic neurotransmission). It is unlikely that NO as such is stored and it is generally accepted that it is synthesized on demand when the nerve endings are excited, although the possibility of the release of a NO-containing molecule protecting it from degradation in the junction has been proposed. Other sources than neurones (interstitial cells, smooth muscle cells) for the NO involved in nonadrenergic noncholinergic inhibitory transmission have also been proposed. Using NADPH diaphorase as a marker for neuronal NOS, deficiency of the nitrergic innervation has been shown in isolated tissue from patients with infantile hypertrophic pyloric stenosis, achalasia and Hirschsprung's disease, suggesting that a lack of NO release might be involved in these disorders. Evidence in favour of nitrergic neurotransmission to smooth muscle has also been obtained in the respiratory and lower urinary tract, the corpora cavernosa and some blood vessels.
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PMID:Nitric oxide in the peripheral nervous system. 754 28