Met-enkephalin is preferentially transported into the peripheral processes of primary afferent fibres in both control and HSV1-driven proenkephalin A overexpressing rats.
The demonstration of preproenkephalin A gene expression in rat dorsal root ganglia has raised the question of the physiological role of met-enkephalin-containing primary afferent fibres. Recently, we showed that systemic infection with a recombinant Herpes simplex virus encoding preproenkephalin A (HSVLatEnk1) yielded a marked increase in the density of met-enkephalin-like material synthesising neurons in rat dorsal root ganglia. This study further investigated the synthesis, transport and release of met-enkephalin-like material in the central and/or peripheral processes of primary afferent fibres in HSVLatEnk1-infected and control rats. In controls, dorsal root ganglia neurons containing met-enkephalin-like material were scarce and only a few positively labelled processes were seen at the peripheral output of the dorsal root ganglia. Met-enkephalin-like material accumulated at the proximal side of ligatured sciatic nerve, but not in ligatured L4-L5 dorsal roots. In HSVLatEnk1-infected rats with numerous somas and fibres stained for met-enkephalin-like material in dorsal root ganglia, met-enkephalin immunoreactive material largely accumulated at the proximal side of the ligatured sciatic nerve and few positively stained fibres were also observed in ligatured dorsal roots. Electrical stimulation of L4-L5 dorsal roots attached to a dorsal slice of the lumbar enlargement produced an overflow of met-enkephalin-like material which was approximately 70% higher in HSVLatEnk1-infected rats compared to controls. At the periphery, subcutaneous microdialysis showed higher basal levels of met-enkephalin-like material in the interstitial fluid of hindpaw plantar area in HSVLatEnk1-infected rats, and electrical stimulation of the ipsilateral sciatic nerve resulted in an approximately three-fold-higher overflow of this material than in control rats. These data demonstrated that met-enkephalin synthesised in dorsal root ganglion of both control and preproenkephalin A overexpressing rats is preferentially transported into the peripheral processes of primary afferent fibres where the peptide reaches a releasable compartment, thus providing a neuronal source of peripheral met-enkephalin.
Antunes bras
J
J
INSERM U288, NeuroPsychoPharmacologie Moléculaire, Cellulaire et Fonctionnelle, C.H.U. Pitié-Salpêtrière, 91 boulevard de l'Hôpital, 75013, Paris, France.
Becker
C
C
Bourgoin
S
S
Lombard
M
M
Cesselin
F
F
Hamon
M
M
Pohl
M
M
D000344:Afferent Pathways / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D004744:Enkephalin, Methionine / Q000378:metabolism*; D004745:Enkephalins / Q000235:genetics / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D005727:Ganglia, Spinal / Q000378:metabolism*; D005822:Genetic Vectors; D006614:Hindlimb / Q000378:metabolism; D008026:Ligation; D009412:Nerve Fibers / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D012016:Reference Values; D012584:Sciatic Nerve / Q000378:metabolism*; D018139:Simplexvirus / Q000235:genetics; D013116:Spinal Cord / Q000378:metabolism
D004745:Enkephalins; D011498:Protein Precursors; C029992:proenkephalin; D004744:Enkephalin, Methionine