Two isoforms of prostaglandin E receptor EP3 subtype : different cooh-terminal domains determine sensitivity to agonist-induced desensitization

摘要: We recently identified two isoforms of mouse prostaglandin (PG) E receptor EP3 subtype, alpha and EP 3 beta, which are produced by alternative splicing different only in the carboxyl-terminal domain (Sugimoto, Y., Negishi, M., Hayashi, Namba, T., Honda, A., Watabe, Hirata, Narumiya, S., Ichikawa, A. (1993) J. Biol. Chem. 268, 2712-2718). examined here agonist-induced desensitization using Chinese hamster ovary cells stably expressing these isoforms. Exposure isoform to PGE2 for 30 min did not change maximal response but increased concentration needed inhibit forskolin-induced cAMP accumulation cells. Further exposure this suppressed as well sensitivity a time-dependent manner; after 24-h exposure, it elicited 50% control Consistent with results, short term sequestered away from cell surface long incubation decreased total number In contrast, beta affect its dose-response curve PGE2, no sequestration or decrease was observed isoform. Thus, domains, desensitization.