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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Enteric inhibitory neural regulation of human colonic circular muscle: role of nitric oxide.

BACKGROUND: Nitric oxide and an apamin-sensitive transmitter may both contribute to neural inhibition in the human colon. The present study investigated the role of NO in regulating spontaneous rhythmic contractions and examined NO-dependent and independent components of neurally evoked hyperpolarization in the human colon. METHODS: Mechanical and electrical activity were recorded from isolated circular muscle strips. RESULTS: Rhythmic contractions were inhibited by nerve stimulation. This response was reduced by apamin, oxyhemoglobin, and L-NG-nitro arginine methyl ester (L-NAME). Electrical recording revealed two components of neurally evoked hyperpolarization: a fast hyperpolarization resulting from a single stimulus and a sustained hyperpolarization that developed with repetitive stimulation. Fast hyperpolarization was not affected by L-NAME or oxyhemoglobin but was significantly reduced by apamin. The sustained hyperpolarization was reduced by L-NAME or apamin. Exogenous NO and the P2y receptor agonist 2-methylthio adenosine 5'-triphosphate (2-MATP) inhibited spontaneous contractions and produced hyperpolarization. Apamin reduced the effects of 2-MATP but not those of NO. CONCLUSIONS: The results support the concept that the inhibitory neurotransmission in the human colon involves two transmitters. A single stimulus results in an apamin-sensitive response. With multiple stimuli, a NO-dependent response develops and sums with the apamin-sensitive mechanism, producing sustained hyperpolarization and inhibition of contractions.[1]


  1. Enteric inhibitory neural regulation of human colonic circular muscle: role of nitric oxide. Keef, K.D., Du, C., Ward, S.M., McGregor, B., Sanders, K.M. Gastroenterology (1993) [Pubmed]
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