Isolated dorsal root ganglion neurones inhibit receptor-dependent adenylyl cyclase activity in associated glial cells
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AbstractBackground and Purpose Hyper-nociceptive PGE2 EP4 receptors and prostacyclin (IP) receptors are present in adult rat dorsal root ganglion (DRG) neurones and glial cells in culture. The present study has investigated the cell-specific expression of two other Gs-protein coupled hyper-nociceptive receptor systems: beta-adrenoceptors and calcitonin gene-related peptide (CGRP) receptors in isolated DRG cells and has examined the influence of neuroneglial cell interactions in regulating adenylyl cyclase (AC) activity. Experimental Approach Agonist-stimulated AC activity was determined in mixed DRG cell cultures from adult rats and compared with activity in DRG neurone-enriched cell cultures and pure DRG glial cell cultures. Key Results Pharmacological analysis showed the presence of Gs-coupled beta 2-adrenoceptors and CGRP receptors, but not beta 1-adrenoceptors, in all three DRG cell preparations. Agonist-stimulated AC activity was weakest in DRG neurone-enriched cell cultures. DRG neurones inhibited IP receptor-stimulated glial cell AC activity by a process dependent on both cellcell contact and neurone-derived soluble factors, but this is unlikely to involve purine or glutamine receptor activation. Conclusions and Implications Gs-coupled hyper-nociceptive receptors are readily expressed on DRG glial cells in isolated cell cultures and the activity of CGRP, EP4 and IP receptors, but not beta 2-adrenoceptors, in glial cells is inhibited by DRG neurones. Studies using isolated DRG cells should be aware that hyper-nociceptive ligands may stimulate receptors on glial cells in addition to neurones, and that variable numbers of neurones and glial cells will influence absolute measures of AC activity and affect downstream functional responses.
All Author(s) ListNg KY, Yeung BHS, Wong YH, Wise H
Journal nameBritish Journal of Pharmacology
Detailed descriptionTo ORKTS: doi: 10.1111/j.1476-5381.2012.02177.x
Volume Number168
Issue Number3
PublisherWiley: 12 months
Pages746 - 760
LanguagesEnglish-United Kingdom
KeywordscAMP; CGRP receptors; dorsal root ganglion cells; EP4 receptors; IP receptors; neurone-glial interactions; primary sensory neurones; ss-adrenoceptors
Web of Science Subject CategoriesPharmacology & Pharmacy; PHARMACOLOGY & PHARMACY

Last updated on 2020-06-07 at 00:40