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.
Keef
K D
KD
Department of Physiology, University of Nevada School of Medicine, Reno.
Du
C
C
Ward
S M
SM
McGregor
B
B
Sanders
K M
KM
D000200:Action Potentials / Q000502:physiology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D001030:Apamin / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003106:Colon / Q000294:innervation / Q000502:physiology*; D004594:Electrophysiology; D006801:Humans; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000294:innervation / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester; D009474:Neurons / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D010108:Oxyhemoglobins / Q000494:pharmacology; D009435:Synaptic Transmission / Q000502:physiology; D013873:Thionucleotides / Q000494:pharmacology
D018377:Neurotransmitter Agents; D010108:Oxyhemoglobins; D013873:Thionucleotides; D001030:Apamin; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester; C008501:2-methylthio-ATP