Cannabinoid CB1 receptor activation stimulates neurite outgrowth and inhibits capsaicin-induced Ca2+ influx in an in vitro model of diabetic neuropathy

Fan Zhang, Sarat C. Challapalli, Paula J. W. Smith*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Cannabinoid CB1 receptors mediate, in part, the neuroprotectant properties of endocannabinoids, and altered signalling via the CB1 receptor may contribute to the pathogenesis of diabetic neuropathy. We investigated CB1 receptor function in PC12 cells differentiated into a neuronal phenotype with nerve growth factor (NGF, 50 ng/ml) in 5.5 and 50 mM concentrations of glucose. High glucose was associated with impaired NGF-induced neurite outgrowth (P <0.01; n = 185-218) and reduced expression of CB1 receptor mRNA (P <0.01; n = 6) on day 6 of culture. Whilst treatment of hyperglycemic cells with HU210 (0.03-3 mu M) increased neurite length in a concentration-dependent manner (P <0.01; n = 136-218), CB1 receptor expression was not significantly altered by chronic agonist stimulation (P = 0.32; n = 6 per group). Application of the CB1 agonist HU210 (1 mu M) inhibited capsaicin-induced calcium transients to a similar degree in cells cultured in high glucose (40%) versus normal (43%) (P <0.05: n = 33-50). HU210-mediated rescue of neurite outgrowth and inhibition of calcium influx was blocked by the selective CB1 antagonist AM251 (1 mu M), but not by the selective CB2 antagonist AM630 (1 mu M), confirming the role of CB1 receptors. High glucose treatment did not significantly elevate endocannabinoid levels. These results suggest that high glucose concentrations are associated with decreased expression, but preserved function of CB1 receptors in nerve cells. (C) 2009 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)88-96
Number of pages9
JournalNeuropharmacology
Volume57
Issue number2
DOIs
Publication statusPublished - Aug 2009

Keywords

  • Cannabinoid
  • CB1
  • Glucose
  • Diabetic neuropathy
  • TRPV1
  • PC12 cells
  • VANILLOID VR1 RECEPTOR
  • PC12 CELLS
  • CARDIORESPIRATORY REFLEXES
  • TACTILE ALLODYNIA
  • EXPRESSION
  • PATHWAY
  • DIFFERENTIATION
  • OBESITY
  • RATS
  • MICE

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