Premium
Comparative desensitization of the human 5‐HT 2A and 5‐HT 2C receptors expressed in the human neuroblastoma cell line SH‐SY5Y
Author(s) -
Briddon S.J.,
Leslie R.A.,
Elliott J.M.
Publication year - 1998
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0702145
Subject(s) - receptor , desensitization (medicine) , 5 ht receptor , endocrinology , medicine , 5 ht2c receptor , receptor antagonist , serotonin , homologous desensitization , inositol phosphate , antagonist , biology , cell culture , chemistry , inositol , genetics
1 We have used previously characterized clones of the human neuroblastoma cell line, SH‐SY5Y, constitutively expressing either the human 5‐HT 2A or 5‐HT 2C receptor to compare their desensitization profiles after exposure to 5‐HT. 2 5‐HT stimulated [ 3 H]‐inositol phosphate ([ 3 H]‐IP x ) production at both the 5‐HT 2C (pEC 50 =8.03±0.15) and 5‐HT 2A receptors (pEC 50 =7.15±0.08), with maximal responses occurring after exposure to 1 μ M and 10 μ M 5‐HT, respectively. 3 Exposure of cells to maximally effective concentrations of 5‐HT caused time‐ and concentration‐dependent desensitization of [ 3 H]‐IP x formation. The 5‐HT 2A response desensitized slower (t 1/2 =110 min) and with lower sensitivity than that of the 5‐HT 2C receptor (t 1/2 =12.5 min). In each case, desensitization was blocked by co‐administration of a specific receptor antagonist. Following exposure to 10 μ M 5‐HT for 2 h, both receptors exhibited extensive desensitization, with subsequent responses to 5‐HT reduced by more than 80%. 4 5‐HT stimulated Ins(1,4,5)P 3 production with a potency similar to that for [ 3 H]‐IP x production at each receptor. In both cases Ins(1,4,5)P 3 levels peaked rapidly then returned to basal level within a short time. This peak consistently occurred earlier for the 5‐HT 2C receptor (5 s) than for the 5‐HT 2A receptor (20 s). 5 Prior exposure of SH‐SY5Y/5‐HT 2C cells to 5‐HT (1 μ M /15 min) caused a significant decrease in the 5‐HT‐stimulated peak in Ins(1,4,5)P 3 levels whereas no such change occurred in SH‐SY5Y/5‐HT 2A cells following exposure to 10 μ M 5‐HT for 15 min. 6 These results indicate that the human 5‐HT 2A and 5‐HT 2C receptors both exhibit desensitization at the level of inositol phosphate formation when expressed in the same cellular environment, with the 5‐HT 2C receptor being more sensitive to 5‐HT‐mediated desensitization than the 5‐HT 2A receptor.British Journal of Pharmacology (1998) 125 , 727–734; doi: 10.1038/sj.bjp.0702145