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

Leonid G. Ermilov, Philip F. Schmalz, Steven M. Miller, Joseph H. Szurszewski

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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 PNCAP-eqic pathway, operated through PAC1-Rs, in controlling the colon-IMG reflex.

Original languageEnglish (US)
Pages (from-to)231-247
Number of pages17
JournalJournal of Physiology
Volume560
Issue number1
DOIs
StatePublished - Oct 1 2004

Fingerprint

Adenylyl Cyclases
Ganglia
Reflex
Guinea Pigs
Colon
Peptides
Pituitary Adenylate Cyclase-Activating Polypeptide
Vasoactive Intestinal Peptide
Neurons
Pituitary Adenylate Cyclase-Activating Polypeptide Receptors
Excitatory Postsynaptic Potentials
Nerve Endings
Spinal Ganglia
Dendrites
Action Potentials
Radioimmunoassay

ASJC Scopus subject areas

  • Physiology

Cite this

PACAP modulation of the colon-inferior mesenteric ganglion reflex in the guinea pig. / Ermilov, Leonid G.; Schmalz, Philip F.; Miller, Steven M.; Szurszewski, Joseph H.

In: Journal of Physiology, Vol. 560, No. 1, 01.10.2004, p. 231-247.

Research output: Contribution to journalArticle

Ermilov, Leonid G. ; Schmalz, Philip F. ; Miller, Steven M. ; Szurszewski, Joseph H. / PACAP modulation of the colon-inferior mesenteric ganglion reflex in the guinea pig. In: Journal of Physiology. 2004 ; Vol. 560, No. 1. pp. 231-247.
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