Present address: Department of Physiology, Shanghai Jiaotong University School of Medicine, 227 South Chongqing Road, Shanghai, P.R. China 200025.
Src family kinases mediate the inhibition of substance P release in the rat spinal cord by μ-opioid receptors and GABAB receptors, but not α2 adrenergic receptors
Article first published online: 18 AUG 2010
European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd. No claim to original US government works
European Journal of Neuroscience
Volume 32, Issue 6, pages 963–973, September 2010
How to Cite
Zhang, G., Chen, W. and Marvizón, J. C. G. (2010), Src family kinases mediate the inhibition of substance P release in the rat spinal cord by μ-opioid receptors and GABAB receptors, but not α2 adrenergic receptors. European Journal of Neuroscience, 32: 963–973. doi: 10.1111/j.1460-9568.2010.07335.x
- Issue published online: 17 SEP 2010
- Article first published online: 18 AUG 2010
- Received 14 January 2010, revised 22 April 2010, accepted 19 May 2010
- calcium channel;
- dorsal horn;
- neurokinin 1 receptor;
- primary afferent
GABAB, μ-opioid and adrenergic α2 receptors inhibit substance P release from primary afferent terminals in the dorsal horn. Studies in cell expression systems suggest that μ-opioid and GABAB receptors inhibit transmitter release from primary afferents by activating Src family kinases (SFKs), which then phosphorylate and inhibit voltage-gated calcium channels. This study investigated whether SFKs mediate the inhibition of substance P release by these three receptors. Substance P release was measured as neurokinin 1 receptor (NK1R) internalization in spinal cord slices and in vivo. In slices, NK1R internalization induced by high-frequency dorsal root stimulation was inhibited by the μ-opioid agonist DAMGO and the GABAB agonist baclofen. This inhibition was reversed by the SFK inhibitor PP1. NK1R internalization induced by low-frequency stimulation was also inhibited by DAMGO, but PP1 did not reverse this effect. In vivo, NK1R internalization induced by noxious mechanical stimulation of the hind paw was inhibited by intrathecal DAMGO and baclofen. This inhibition was reversed by intrathecal PP1, but not by the inactive PP1 analog PP3. PP1 produced no effect by itself. The α2 adrenergic agonists medetomidine and guanfacine produced a small but statistically significant inhibition of NK1R internalization induced by low-frequency dorsal root stimulation. PP1 did not reverse the inhibition by guanfacine. These results show that SFKs mediate the inhibition of substance P release by μ-opioid and GABAB receptors, but not by α2 receptors, which is probably mediated by the binding of G protein βγ subunits to calcium channels.