Prolonged inhibition of 5-HT₃ receptors by palonosetron results from surface receptor inhibition rather than inducing receptor internalization.

ABSTRACT:

Background and purpose

The 5-HT₃ receptor antagonist palonosetron is an important treatment for emesis and nausea during cancer therapy. Its clinical efficacy may result from its unique binding and clearance characteristics and receptor down-regulation mechanisms. We investigated the mechanisms by which palonosetron exerts its long-term inhibition of 5-HT₃ receptors for a better understanding of its clinical efficacy.

Experimental approach

Cell surface receptors (recombinantly expressed 5HT₃A or 5HT₃AB in COS-7 cells) were monitored using [³H]granisetron binding and ELISA after exposure to palonosetron. Receptor endocytosis was investigated using immunofluorescence microscopy.

Key results

Chronic exposure to palonosetron reduced the number of available cell surface [³

SUBMITTER: Hothersall JD 

PROVIDER: S-EPMC3831706 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature