Isolated dorsal root ganglion neurones inhibit receptor-dependent adenylyl cyclase activity in associated glial cells
Version of Record online: 16 JAN 2013
© 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society
British Journal of Pharmacology
Volume 168, Issue 3, pages 746–760, February 2013
How to Cite
Ng, K., Yeung, B., Wong, Y. and Wise, H. (2013), Isolated dorsal root ganglion neurones inhibit receptor-dependent adenylyl cyclase activity in associated glial cells. British Journal of Pharmacology, 168: 746–760. doi: 10.1111/j.1476-5381.2012.02177.x
- Issue online: 16 JAN 2013
- Version of Record online: 16 JAN 2013
- Accepted manuscript online: 24 AUG 2012 08:06AM EST
- Manuscript Accepted: 15 AUG 2012
- Manuscript Revised: 6 JUL 2012
- Manuscript Received: 10 NOV 2011
- Research Grants Council of the Hong Kong Special Administrative Region. Grant Number: CUHK4516/06 M
- The Chinese University of Hong Kong. Grant Number: CUHK2041446
- CGRP receptors;
- dorsal root ganglion cells;
- EP4 receptors;
- IP receptors;
- neurone–glial interactions;
- primary sensory neurones;
Background 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: β-adrenoceptors and calcitonin gene-related peptide (CGRP) receptors in isolated DRG cells and has examined the influence of neurone–glial cell interactions in regulating adenylyl cyclase (AC) activity.
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.
Pharmacological analysis showed the presence of Gs-coupled β2-adrenoceptors and CGRP receptors, but not β1-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 cell–cell 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 β2-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.