The Journal of Neuroscience, July 15, 1998, 18(14):5285-5293
Vasoactive Intestinal Peptide Enhances Its Own Expression in
Sympathetic Neurons after Injury
Robert P.
Mohney and
Richard E.
Zigmond
Department of Neurosciences, Case Western Reserve University,
Cleveland Ohio 44106-4975
Neurons in the adult rat superior cervical sympathetic ganglion
(SCG) dramatically increase their content of vasoactive intestinal peptide (VIP) and its mRNA after axotomy in vivo and
after explantation. Because the VIP gene contains a functional cAMP
response element, the effects of cAMP-elevating agents on VIP
expression were examined. VIP, forskolin, or isoproterenol increased
cAMP accumulation in explanted ganglia. Secretin, a peptide chemically
related to VIP, or forskolin increased VIP levels above those seen in
ganglia cultured in control medium, whereas treatment with VIP or
secretin increased the level of peptide histidine isoleucine (PHI), a
peptide coded for by the same mRNA that encodes VIP. VIP or forskolin also increased VIP-PHI mRNA. In contrast, isoproterenol did not alter
levels of VIP, PHI, or VIP-PHI mRNA. Although VIP or forskolin increased cAMP levels in both dissociated neurons and in non-neuronal cells, isoproterenol significantly stimulated cAMP accumulation only in
the latter. VIP6-28 was an effective antagonist of the
actions of exogenous VIP on cAMP and VIP-PHI mRNA in neuron-enriched cultures. When adult SCG explants were cultured in defined medium, endogenous VIP immunoreactivity was released. When VIP6-28 was added to such cultures, it significantly inhibited the increase in
VIP-PHI mRNA that normally occurs. These data indicate that VIP, or a
closely related molecule, produced by adult neurons after injury can
enhance the expression of VIP. Such a mechanism may prolong the period
during which VIP is elevated after axonal damage. The possibility is
also discussed that, because VIP is present in preganglionic neurons in
normal animals, its release during periods of increased sympathetic
nerve activity could alter VIP expression in the SCG.
Key words:
cAMP; isoproterenol; secretin; superior cervical
ganglion; sympathetic; vasoactive intestinal peptide; VIP
antagonist
Copyright © 1998 Society for Neuroscience 0270-6474/98/18145285-09$05.00/0