Tropisetron upregulates cannabinoid CB1 receptors in cerebellar granule cells: Possible involvement of calcineurin

Tropisetron attenuates amyloid‐beta‐induced inflammatory and apoptotic responses in rats

“…We also observed recently in cultured cerebellar granule cells that tropisetron dose dependently inhibited the depolarization‐induced phosphatase activity of calcineurin. Of note, the cultured cells were devoid of 5‐HT 3 receptors, pointing to a receptor‐independent mechanism for calcineurin inhibitory action of tropisetron . Our present data indicate that alongside its receptor‐independent effects, tropisetron can exert calcineurin suppressive activity in vivo through binding to and antagonizing the 5‐HT 3 receptors.…”

“…Moreover, we found that pretreatment with tropisetron significantly improved neurological deficits and diminished leucocyte transmigration into the brain, TNF-a level and brain infarction in a murine model of embolic stroke [13]. Our latest investigation revealed that tropisetron potently inhibits calcineurin activity in cerebellar granule neurons [14]. Calcineurin is a Ca 2+ /calmodulin-dependent protein phosphatase that upregulates numerous cytokines and pro-inflammatory factors in immune cells [15].…”

Tropisetron ameliorates early diabetic nephropathy in streptozotocin‐induced diabetic rats

“…Our data were in agreement with this study by Gooch et al ., as urine volume in tropisetron‐treated animals and the STZ + tropisetron group was increased compared with the untreated control group and the STZ + tropisetron group, respectively (Table ). Moreover, it was shown that tropisetron potently inhibited calcineurin activity in cerebellar granule cell culture . Therefore, we believe that the main reason for increased GFR in the STZ + tropisetron group is inhibition of calcineurin‐mediated regulation of aquaporin 2 and a very significant increase in the UFR.…”

“…They showed that calcineurin plays a very important role in early DN, and cyclosporine A can significantly improve this injury. Therefore, we investigated whether tropisetron, as a safer calcineurin inhibitor, can act similarly. We found that tropisetron can attenuate DN not only through calcineurin inhibition (data not published) but also by suppressing oxidative stress and some inflammatory cytokines.…”

5-HT3 Receptor Antagonists in Neurologic and Neuropsychiatric Disorders: The Iceberg Still Lies beneath the Surface

“…Intriguingly, 5-HT 3 R antagonists and cannabinoids share several pharmacological properties such as analgesic, anti-inflammatory, and antiemetic effects. These common properties imply that 5-HT 3 Rs can be closely involved in various pharmacological aspects of cannabinoids, and this dimension is of relevance for designing cannabinoid derivatives with fewer psychoactive effects (Rahimian et al, 2011b). Steroids are also noncompetitive inhibitors of 5-HT 3 R at pharmacological concentrations (Walstab et al, 2010;Davies, 2011).…”