| Autor: |
Rodriguez-Pena MS; Leiden/Amsterdam Center for Drug Research, Division of Medicinal Chemistry, Faculty of Chemistry, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands., Timmerman H, Leurs R |
| Jazyk: |
angličtina |
| Zdroj: |
British journal of pharmacology [Br J Pharmacol] 2000 Dec; Vol. 131 (8), pp. 1707-15. |
| DOI: |
10.1038/sj.bjp.0703676 |
| Abstrakt: |
To evaluate the role of G-protein-coupled receptor kinases (GRK) in the desensitization of the histamine H(2) receptor, the H(2) receptor was transiently cotransfected with GRK2, 3, 5 or 6 in COS-7 cells and the cyclic AMP levels in response to histamine were studied. Coexpression of the H(2) receptor with GRK2 and 3 significantly decreased both the basal cyclic AMP levels and the cyclic AMP response to 100 microM histamine. Moreover, preincubation with 100 microM histamine desensitized the H(2) receptor response to 53+/-8%. Coexpression of GRK2 and 3 increased the H(2) receptor desensitization to 27+/-4% and 24+/-4% respectively. No effect on either cyclic AMP response or desensitization was found when GRK5, GRK6 or dominant negative mutants of GRK2 or 3 (GRK2K(220)R and GRK3K(220)R) were coexpressed. To study the role of the C-terminal tail in the GRK-mediated desensitization of the H(2) receptor, three truncations of C-tail were constructed: H(2)T295, H(2)T307 and H(2)T341. H(2)T307 and 341 H(2)T341 expressed and responded normally to 100 microM histamine. The interaction of the H(2) receptor with GRK2 and 3 was also not altered upon truncation of the C-terminal tail. These findings strongly suggest a role of GRK2 and 3 in the desensitization of the H(2) receptor. Furthermore, the finding that C-terminal truncations of the H(2) receptor did not abolish the effect of GRK2 and 3 suggests that the C-terminus is not involved in the GRK mediated desensitization of the histamine H(2) receptor. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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