Journal of Neuroscience, Vol 14, 3540-3547, Copyright © 1994 by Society for Neuroscience
VIP modulates neuronal nicotinic acetylcholine receptor function by a cyclic AMP-dependent mechanism
D Gurantz, AT Harootunian, RY Tsien, VE Dionne and JF Margiotta
Department of Pharmacology, University of California at San Diego, La Jolla 92093.
Neuronal nicotinic ACh receptors (AChRs) mediate synaptic transmission
throughout the nervous system, and are regulated by cellular processes and
interactions that include second messenger signaling pathways. In the case
of chick ciliary ganglion neurons, activation of the cAMP- dependent
signaling pathway with cAMP analogs enhances ACh sensitivity in a manner
consistent with an increase in the number of functional nicotinic
receptors. We have now identified vasoactive intestinal peptide (VIP) as a
neuromodulator or "first messenger" in the cAMP- mediated pathway that
regulates neuronal AChRs. Using cAMP imaging and biochemical detection
assays, we find that bath application of VIP elevates intracellular cAMP in
freshly isolated ciliary ganglion neurons within minutes. The VIP treatment
also enhances neuronal ACh sensitivity assessed with whole-cell recording.
The enhanced ACh sensitivity produced by VIP appears with a short latency,
similar to that associated with the increase in cAMP, and is not additive
with the enhanced ACh sensitivity produced by bath application of a cAMP
analog. In contrast, calcitonin gene-related peptide (CGRP), known to
regulate muscle nicotinic AChRs via a cAMP-dependent pathway, has no
detectable effect on levels of either cAMP or ACh sensitivity in the
neurons. The results indicate that VIP enhances the ACh sensitivity of
ciliary ganglion neurons via a cAMP-dependent signaling pathway, presumably
by interaction with a specific receptor. Since VIP-like immunoreactivity is
present in the presynaptic nerve terminals of avian ciliary ganglia, a
VIP-like peptide could modulate AChRs in vivo.
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