A study found that mice without a PAF receptor antagonist developed many skin tumors when exposed to UV light, while mice with a PAF receptor antagonist developed fewer tumors. Additional experiments showed that PAF and serotonin receptor antagonists blocked immune suppression caused by cis-UCA, and that cis-UCA and 5-HT share binding sites on the serotonin receptor. Blocking the 5-HT receptor with antagonists, antibodies, or by blocking cis-UCA inhibited cis-UCA and UV-induced immune suppression in vivo.

1. Results and figures Sarah and Waleed

2. PAF receptor antagonist inhibited UV-induced skin cancer induction in mice Mice without PAF antagonist developed many tumours Mice with PAF antagonist developed fewer tumours (P<0.001 Mann-Whitney U-test) Ulrich S. (2007); Molecular Carcinogenesis 46: 629-33

3. Do PAF receptor antagonists inhibit cis-UCA induced immune suppression? YES! And so does the 5-HT receptor antagonist, ketanserin!

4. Copyright ©2006 by the National Academy of Sciences Walterscheid, Jeffrey P. et al. (2006) Proc. Natl. Acad. Sci. USA 103, 17420-17425 PAF and serotonin receptor antagonists block cis-UCA- induced immune suppression * denotes P<0.001 PAF receptor antagonists

5. Do cis-UCA and 5-HT share a receptor?

6. Copyright ©2006 by the National Academy of Sciences Walterscheid, Jeffrey P. et al. (2006) Proc. Natl. Acad. Sci. USA 103, 17420-17425 5-HT and cis-UCA share binding sites

8. Copyright ©2006 by the National Academy of Sciences Walterscheid, Jeffrey P. et al. (2006) Proc. Natl. Acad. Sci. USA 103, 17420-17425 Saturation binding of cis-UCA to L-NCG-5HT 2A cells

9. Copyright ©2006 by the National Academy of Sciences Walterscheid, Jeffrey P. et al. (2006) Proc. Natl. Acad. Sci. USA 103, 17420-17425 cis-UCA activates intracellular calcium flux via the serotonin receptor

10. Are Cis-UCA and 5-HT structurally similar? YES Do cis-UCA and 5-HT share a receptor? Competitive Binding Studies /Calcium Mobilization Immunoprecipitation YES

11. Copyright ©2006 by the National Academy of Sciences Walterscheid, Jeffrey P. et al. (2006) Proc. Natl. Acad. Sci. USA 103, 17420-17425 Immunoprecipitation study

12. Are Cis-UCA and 5-HT structurally similar? YES Do cis-UCA and 5-HT share a receptor? YES Immunoprecipitation Does blocking 5-HT binding inhibits UV/cis-UCA induced immunosuppression? In vivo studies

13. Copyright ©2006 by the National Academy of Sciences Walterscheid, Jeffrey P. et al. (2006) Proc. Natl. Acad. Sci. USA 103, 17420-17425 Inhibition of cis-UCA- and UV-induced immune suppression with selective 5-HT receptor antagonists, anti-cis-UCA antibody, or anti-5-HT antibody *denotes P<0.01

14. Sample size? n=5

15. Are Cis-UCA and 5-HT structurally similar? YES Do cis-UCA and 5-HT share a receptor? YES Does blocking 5-HT binding inhibits UV/cis-UCA induced immunosuppression? YES In vivo studies

16. Conclusions Immunosuppressive effects of cis-UCA and UV radiation are mediated by activation of the 5-HT 2A receptor Potential for using 5-HT receptor antagonists to prevent skin cancer by blocking UV-induced immune suppression, but further studies are needed.