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This Article Full Text Full Text (PDF) All Versions of this Article: 560/1/231    most recent jphysiol.2004.070060v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ermilov, L. G Articles by Szurszewski, J. H Search for Related Content PubMed PubMed Citation Articles by Ermilov, L. G Articles by Szurszewski, J. H

¹ Department of Physiology and Biomedical Engineering
² Enteric NeuroScience Program
³ Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, 200 First Street, SW, Rochester, MN 55905 USA

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.

(Received 15 June 2004; accepted after revision 27 July 2004; first published online 29 July 2004)
Corresponding author J. H. Szurszewski: Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA. Email: gijoe{at}mayo.edu

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