Vasoactive intestinal peptide enhances its own expression in sympathetic neurons after injury.
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.
Mohney
R P
RP
Department of Neurosciences, Case Western Reserve University, Cleveland Ohio 44106-4975, USA.
Zigmond
R E
RE
D000818:Animals; D019771:Axotomy; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D005246:Feedback; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009924:Organ Culture Techniques; D010446:Peptide Fragments / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical; D017783:Superior Cervical Ganglion / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D014660:Vasoactive Intestinal Peptide / Q000096:biosynthesis / Q000494:pharmacology*
D010446:Peptide Fragments; D012333:RNA, Messenger; C113198:vasoactive intestinal peptide (6-28); D005576:Colforsin; D014660:Vasoactive Intestinal Peptide; D000242:Cyclic AMP; D007545:Isoproterenol