Glucose concentration in culture medium affects mRNA expression of TRPV۱ and CB۱ receptors and changes capsaicin toxicity in PC۱۲ cells

Objective (s):Hyperglycemia is widely recognized as the underlying cause for some debilitating conditions in diabetic patients. The role of cannabinoid CB۱ and vanilloid TRPV۱ receptors and their endogenous agonists, endovanilloids, in diabetic neuropathy is shown in many studies. Here we have used PC۱۲ cell line to investigate the possible influence of glucose concentration in culture medium on cytoprotective or toxic effects of a CB۱ [WIN۵۵ ۲۱۲-۲ (WIN)], or TRPV۱ [Capsaicin (CAS)] agonist. Materials and Methods: Cell viability was tested using the MTT assay. We have also measured TRPV۱ and CB۱ transcripts by real time reverse transcription-polymerase chain reaction while cells were grown in low (۵.۵ mM) and high (۵۰ mM) glucose concentrations. Results:Real time PCR results indicated that high glucose medium increased (P<۰.۰۱) TRPV۱ mRNA and decreased (P <۰.۰۰۱) that of CB۱. Cell culture tests show that hyperglycemic cells are more vulnerable (Dose × Medium, F (۳,۶۳)=۴۱.۵, P<۰.۰۰۱) to the toxic effects of capsaicin compared to those grown in low glucose medium. Conclusion: These findings propose that hyperglycemic conditions may result in neuronal cell death because of inducing a counterbalance between cytotoxic TRPV۱ and cytoprotective CB۱ receptors.

Keywords:

CB۱ , Hyperglycemia , PC۱۲ cells , TRPV۱