PACAP modulation of the colon-inferior mesenteric ganglion reflex in the guinea pig

J Physiol. 2004 Oct 1;560(Pt 1):231-47. doi: 10.1113/jphysiol.2004.070060. Epub 2004 Jul 29.


We investigated the effect of pituitary adenylate cyclase activating peptide (PACAP) on the colon-inferior mesenteric ganglion (IMG) reflex loop in vitro. PACAP27 and PACAP38 applied to the IMG caused a prolonged depolarization and intense generation of fast EPSPs and action potentials in IMG neurones. Activation of PACAP-preferring receptors (PAC1-Rs) with the selective agonist maxadilan or vasoactive intestinal peptide (VIP)/PACAP (VPAC) receptors with VIP produced similar effects whereas prior incubation of the IMG with selective PAC1-R antagonists PACAP6-38 and M65 inhibited the effects of PACAP. Colonic distension evoked a slow EPSP in IMG neurones that was reduced in amplitude by prolonged superfusion of the IMG with either PACAP27, maxidilan, PACAP6-38, M65 or VIP. Activation of IMG neurones by PACAP27 or maxadilan resulted in an inhibition of ongoing spontaneous colonic contractions. PACAP-LI was detected in nerve trunks attached to the IMG and in varicosities surrounding IMG neurones. Cell bodies with PACAP-LI were present in lumbar 2-3 dorsal root ganglia and in colonic myenteric ganglia. Colonic distension evoked release of PACAP peptides in the IMG as measured by radioimmunoassay. Volume reconstructed images showed that a majority of PACAP-LI, VIP-LI and VAChT-LI nerve endings making putative synaptic contact onto IMG neurones and a majority of putative receptor sites containing PAC1-R-LI and nAChR-LI on the neurones were distributed along secondary and tertiary dendrites. These results suggest involvement of a PACAP-ergic pathway, operated through PAC1-Rs, in controlling the colon-IMG reflex.

Publication types

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

MeSH terms

  • Acetylcholine / metabolism
  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Colon / innervation*
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Ganglia, Autonomic / cytology
  • Ganglia, Autonomic / metabolism*
  • Guinea Pigs
  • Immunohistochemistry
  • Insect Proteins / pharmacology
  • Male
  • Membrane Transport Proteins / metabolism
  • Nerve Growth Factors / metabolism
  • Nerve Growth Factors / pharmacology*
  • Neurons, Afferent / drug effects
  • Neurons, Afferent / metabolism
  • Neuropeptides / metabolism
  • Neuropeptides / pharmacology*
  • Neurotransmitter Agents / metabolism
  • Neurotransmitter Agents / pharmacology*
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Pressure
  • Presynaptic Terminals / metabolism
  • Receptors, Cell Surface / agonists
  • Receptors, Cell Surface / antagonists & inhibitors
  • Receptors, Nicotinic / metabolism
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
  • Reflex / drug effects*
  • Reflex / physiology*
  • Vasoactive Intestinal Peptide / metabolism
  • Vasoactive Intestinal Peptide / pharmacology
  • Vesicular Acetylcholine Transport Proteins


  • Insect Proteins
  • Membrane Transport Proteins
  • Nerve Growth Factors
  • Neuropeptides
  • Neurotransmitter Agents
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Receptors, Cell Surface
  • Receptors, Nicotinic
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
  • Vesicular Acetylcholine Transport Proteins
  • maxadilan protein, insect
  • Vasoactive Intestinal Peptide
  • Acetylcholine