Prostaglandin E2 increases the expression of the neurokinin1 receptor in adult sensory neurones in culture: a novel role of prostaglandins.
(1) Peripheral inflammation causes an increase in the proportion of primary afferent neurones that express neurokinin(1) (NK(1)) receptors for substance P (SP). This upregulation may contribute to the neuronal mechanisms of inflammatory pain. The aim of this study was to identify endogenous mediators that stimulate upregulation of NK(1) receptors in dorsal root ganglion (DRG) neurones. Cultured DRG neurones from the adult normal rat were exposed for 2 days to media that contained specific mediators, namely potassium in high concentration, prostaglandin E(2) (PGE(2)), somatostatin (SRIF), and compounds influencing second messenger cascades. After fixation neurones were labelled with an NK(1) receptor antibody. (2) Repetitive addition of the inflammatory mediator PGE(2) or dibutyryl-cyclic adenosine 3',5' monophophate (db-cAMP) to the culture medium enhanced the proportion of neurones with NK(1) receptor-like immunoreactivity from about 12% up to 40%. PGE(2)-induced upregulation was prevented by coadministration of PGE(2) and a protein kinase A inhibitor or SRIF to the medium. High potassium concentration, protein kinase C inhibitors and omission of nerve growth factor from the medium had no effect. (3) In calcium-imaging experiments, bath application of SP evoked increases of the intracellular calcium concentration in about 20% of the neurones. This proportion increased to about 40% after PGE(2)-pretreatment, but the increase was prevented when PGE(2) and SRIF were coadministered to the medium. (4) These data show that the expression of NK(1) receptor-like immunoreactivity in DRG neurones is regulated by the inflammatory mediator PGE(2). This upregulation depends on the intracellular adenylyl cyclase-protein kinase A pathway.
Segond von Banchet
Gisela
G
Institute of Physiology I, University of Jena, Teichgraben 8, D-07740 Jena, Germany.
Scholze
Anita
A
Schaible
Hans-Georg
HG
D000818:Animals; D002478:Cells, Cultured; D015232:Dinoprostone / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000096:biosynthesis* / Q000235:genetics
D011453:Prostaglandins; D018040:Receptors, Neurokinin-1; D015232:Dinoprostone