Journal of Neuroscience, Vol 12, 3717-3728, Copyright © 1992 by Society for Neuroscience
Depolarization increases vasoactive intestinal peptide- and substance P- like immunoreactivities in cultured neonatal and adult sympathetic neurons
Y Sun, MS Rao, SC Landis and RE Zigmond
Department of Neurosciences, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106.
Depolarization has been shown to alter the biosynthesis of a number of
neurotransmitters and neuromodulators. In the rat superior cervical
ganglion (SCG), for example, depolarization has been reported to increase
catecholamine biosynthesis and to decrease the level of substance P. We
have recently found that, although the level of vasoactive intestinal
peptide (VIP)-like immunoreactivity (IR) is normally low in the SCG, it
increases significantly 48 hr after adult ganglia are deafferented in situ
or placed in organ culture. Both manipulations decrease electrical activity
of postganglionic neurons. To determine whether the increases in ganglionic
VIP-IR could be a consequence of decreased depolarization of sympathetic
neurons, the effect of depolarization on the expression of VIP-IR was
examined in organ cultures of neonatal and adult SCG. Depolarization with
elevated K+ (30 mM) or veratridine (1.5 microM) amplified, rather than
blocked, the increases in VIP-IR content seen after 24 hr. Further, it
increased the number of detectable VIP-IR neuronal cell bodies and
processes. The stimulatory effects of veratridine were prevented by TTX.
Since similar changes in expression of VIP-IR were evident in dissociated
cell cultures of the SCG, cell-cell interactions requiring intact
ganglionic architecture are not necessary for altered peptide expression.
Elevating the concentration of Mg2+ blocked the ability of K+ and
veratridine to increase VIP-IR in dissociated cell culture, raising the
possibility that the effects of depolarization on VIP-IR are mediated by
increased Ca2+ entry. The depolarizing conditions that increased VIP- IR
also increased substance P-IR. While higher concentrations of veratridine
(50 microM) blocked the elevation of both VIP- and substance P-IR induced
by explantation, they produced significant neuronal death. Since
depolarization with either 30 mM KCl or 1.5 microM veratridine increases
expression of VIP-IR in neonatal and adult ganglia, decreased
depolarization is unlikely to cause the increases in VIP- and substance
P-IR that occur in culture. Furthermore, our data raise the possibility
that sympathetic nerve activity in vivo can increase expression of these
peptides.
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