Evidence for VIP-induced increase in NO production in myenteric neurons of opossum internal anal sphincter

Am J Physiol. 1996 Mar;270(3 Pt 1):G492-7. doi: 10.1152/ajpgi.1996.270.3.G492.


A significant interaction between vasoactive intestinal polypeptide (VIP) and nitric oxide (NO) has been reported in neurotransmission of the gastrointestinal tract, including the internal anal sphincter (IAS). The exact site of this NO release from the IAS in response to VIP is not known. Studies were carried out to determine the site of this VIP-induced NO release in opossum IAS. NO synthase (NOS) activity was quantitated by determining L--3H-citrulline production from L[3H]arginine in isolated myenteric ganglia and smooth muscle cells of the IAS. L-[3H]citrulline production was determined before and after treatment with either the ganglionic stimulant 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP), VIP, or peptide histidine isoleucine (PHI) in the absence and presence of the neurotoxin tetrodotoxin and the NOS inhibitor NG-nitro-L-arginine (L-NNA). Smooth muscle cells and ganglia were preloaded with L-[3H]arginine for 5 min and treated with VIP for 1 and 5 min. DMPP and VIP caused a significant increase in L-[3H]citrulline formation in myenteric ganglia at both time periods, whereas in smooth muscle cells there was a moderate but significant increase in L-[3H]citrulline production only at 5 min of VIP treatment. VIP-induced relaxation of isolated smooth muscle cells of the IAS was not affected by L-NNA. The increase in NOS activity of myenteric ganglia by DMPP and VIP was sensitive to neurotoxin and the NOS inhibitor. The data suggest that the increase in NO production in response to VIP in the IAS occurs mainly from the myenteric neurons, with some contribution from the smooth muscle cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anal Canal / innervation
  • Anal Canal / physiology*
  • Animals
  • Arginine / analogs & derivatives*
  • Arginine / metabolism
  • Arginine / pharmacology
  • Cells, Cultured
  • Citrulline / metabolism
  • Dimethylphenylpiperazinium Iodide / pharmacology
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Ganglia, Autonomic / physiology
  • In Vitro Techniques
  • Kinetics
  • Muscle Relaxation / drug effects
  • Muscle, Smooth / physiology
  • Myenteric Plexus / drug effects
  • Myenteric Plexus / physiology*
  • Neurons / drug effects
  • Neurons / physiology*
  • Nitric Oxide / biosynthesis*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitroarginine
  • Opossums
  • Peptide PHI / pharmacology
  • Tetrodotoxin / pharmacology
  • Vasoactive Intestinal Peptide / pharmacology*


  • Enzyme Inhibitors
  • Peptide PHI
  • Nitroarginine
  • Citrulline
  • Nitric Oxide
  • Vasoactive Intestinal Peptide
  • Tetrodotoxin
  • Dimethylphenylpiperazinium Iodide
  • Arginine
  • Nitric Oxide Synthase