The effect of inhibitors of receptor internalization on the desensitization and resensitization of three G(s)-coupled receptor responses

1 Many G protein-coupled receptors (GPCRs) are known to internalize followi ng agonist exposure, however the relative importance of this mechanism for the desensitization and resensitization of different GPCRs is unclear. In t he present study, we have pretreated NG108-15 cells with hypertonic sucrose or concanavalin A (con A), to investigate the effects of these inhibitors of internalization on the agonist-induced desensitization and subsequent re sensitization of three G(s)-coupled receptor responses. 2 Incubation of cells with sucrose or con A did not affect subsequent acute agonist stimulation of the A(2A) adenosine receptor or the agonist-induced desensitization of this receptor response. However, the resensitization of the A(2A) adenosine receptor response following agonist removal was abolis hed in the presence of sucrose or con A. 3 Sucrose or con A treatment affected neither the desensitization nor resen sitization of IP-prostanoid receptor responsiveness. On the other hand con A but not sucrose reduced the agonist-induced desensitization of secretin r eceptor responsiveness. However, secretin receptor responsiveness did not r esensitize within the time period studied whether or not inhibitors of inte rnalization were present. 4 These results indicate that receptor internalization appears to subserve different functions for different GPCRs.