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. © 1993.