Molecular mechanisms of pain: serotonin1A receptor agonists trigger transactivation by c-fos of the prodynorphin gene in spinal cord neurons.
By using spinal cord neurons cultured in chemically defined medium, a double labeling procedure, and blockage with antisense oligonucleotides, we show that induction of c-fos and the subsequent transactivation of the prodynorphin gene are coupled events, triggered by serotonin1A receptor agonists. Addition of the specific 1A agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) to the culture, at concentrations similar to that needed for transactivation of the prodynorphin gene, also significantly increases cAMP levels. Furthermore, in rats depleted of serotonin by intrathecal administration of 5,7-dihydroxytryptamine, the induction of prodynorphin after noxious stimulation is dramatically decreased compared with the induction in sham-operated rats. These results suggest that the expression of the prodynorphin gene in spinal cord is under the control of the raphe-spinal efferents containing serotonin.
Lucas
J J
JJ
Instituto Cajal de Neurociencia, Consejo Superior Investigaciones Científicas, Madrid, Spain.
Mellström
B
B
Colado
M I
MI
Naranjo
J R
JR
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D003714:Denervation; D004745:Enkephalins / Q000235:genetics*; D005786:Gene Expression Regulation; D005796:Genes; D008969:Molecular Sequence Data; D009474:Neurons / Q000502:physiology; D015345:Oligonucleotide Probes / Q000235:genetics; D010146:Pain / Q000503:physiopathology*; D011498:Protein Precursors / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos / Q000502:physiology*; D011985:Receptors, Serotonin / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology*; D015533:Transcriptional Activation
D004745:Enkephalins; D015345:Oligonucleotide Probes; D011498:Protein Precursors; D016760:Proto-Oncogene Proteins c-fos; D011985:Receptors, Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C033660:preproenkephalin