PACAP modulation of the colon-inferior mesenteric ganglion reflex in the guinea pig.
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.
Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
Leonid G
LG
Ermilov
Philip F
PF
Schmalz
Steven M
SM
Miller
Joseph H
JH
Szurszewski
D000109:Acetylcholine / Q000378:metabolism; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D003106:Colon / Q000294:innervation*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005725:Ganglia, Autonomic / Q000166:cytology / Q000378:metabolism*; D006168:Guinea Pigs; D007150:Immunohistochemistry; D019476:Insect Proteins / Q000494:pharmacology; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism / Q000494:pharmacology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000378:metabolism / Q000494:pharmacology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011312:Pressure; D017729:Presynaptic Terminals / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000819:agonists / Q000037:antagonists & inhibitors; D011978:Receptors, Nicotinic / Q000378:metabolism; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D012018:Reflex / Q000187:drug effects* / Q000502:physiology*; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism / Q000494:pharmacology; D050494:Vesicular Acetylcholine Transport Proteins
D019476:Insect Proteins; D026901:Membrane Transport Proteins; D009414:Nerve Growth Factors; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011956:Receptors, Cell Surface; D011978:Receptors, Nicotinic; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D050494:Vesicular Acetylcholine Transport Proteins; C069147:maxadilan protein, insect; D014660:Vasoactive Intestinal Peptide; D000109:Acetylcholine