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 PACAP-ergic pathway, operated through PAC1-Rs, in controlling the colon-IMG reflex.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acetylcholine / metabolism
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Action Potentials / drug effects
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Action Potentials / physiology
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Animals
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Colon / innervation*
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Excitatory Postsynaptic Potentials / drug effects
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Excitatory Postsynaptic Potentials / physiology
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Ganglia, Autonomic / cytology
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Ganglia, Autonomic / metabolism*
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Guinea Pigs
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Immunohistochemistry
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Insect Proteins / pharmacology
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Male
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Membrane Transport Proteins / metabolism
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Nerve Growth Factors / metabolism
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Nerve Growth Factors / pharmacology*
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Neurons, Afferent / drug effects
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Neurons, Afferent / metabolism
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Neuropeptides / metabolism
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Neuropeptides / pharmacology*
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Neurotransmitter Agents / metabolism
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Neurotransmitter Agents / pharmacology*
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Pituitary Adenylate Cyclase-Activating Polypeptide
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Pressure
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Presynaptic Terminals / metabolism
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Receptors, Cell Surface / agonists
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Receptors, Cell Surface / antagonists & inhibitors
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Receptors, Nicotinic / metabolism
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Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide
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Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
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Reflex / drug effects*
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Reflex / physiology*
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Vasoactive Intestinal Peptide / metabolism
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Vasoactive Intestinal Peptide / pharmacology
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Vesicular Acetylcholine Transport Proteins
Substances
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Insect Proteins
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Membrane Transport Proteins
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Nerve Growth Factors
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Neuropeptides
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Neurotransmitter Agents
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Pituitary Adenylate Cyclase-Activating Polypeptide
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Receptors, Cell Surface
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Receptors, Nicotinic
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Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide
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Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
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Vesicular Acetylcholine Transport Proteins
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maxadilan protein, insect
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Vasoactive Intestinal Peptide
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Acetylcholine