JPET

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Pleus, R. C.
Right arrow Articles by Bylund, D. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pleus, R. C.
Right arrow Articles by Bylund, D. B.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*PINDOLOL

Desensitization and down-regulation of the 5-hydroxytryptamine1B receptor in the opossum kidney cell line

RC Pleus and DB Bylund

Department of Pharmacology, University of Nebraska Medical Center, Omaha.

In the opossum kidney cell line the 5-hydroxytryptamine (serotonin; 5- HT)1B receptor is negatively coupled to adenylyl cyclase via a Gi protein. Preincubation of opossum kidney cell line cell monolayers with 5-HT resulted in 5-HT1B receptor-mediated desensitization expressed as a 4-fold rightward shift of the dose-response curve and a 10 to 29% decrease of maximal inhibition of forskolin-stimulated cyclic AMP production. These moderate decreases in potency and efficacy were concentration- and time-dependent. Maximal desensitization occurred with 3 hr of 5-HT preincubation. Preincubation with 5-HT caused no change in the potency or efficacy of alpha-2 adrenergic agonist- mediated inhibition of forskolin-stimulated cyclic AMP production. Therefore, the desensitization caused by 5-HT preincubation appears to be homologous. Down-regulation of the 5-HT1B receptor, assessed with the high affinity radioligand [125I]iodocyanopindolol, also occurred, and was concentration- and time-dependent. Maximum down-regulation of 40% occurred after 20 hr of exposure to 10 microM 5-HT. These results demonstrate that, like other receptors coupled to the inhibition of adenylyl cyclase, exposure of 5-HT1B receptors to an agonist causes desensitization of the functional response followed by down-regulation of the receptor.

Volume 261, Issue 1, pp. 271-277, 04/01/1992
Copyright © 1992 by American Society for Pharmacology and Experimental Therapeutics




This article has been cited by other articles:


Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
N. H. Garcia, T. J. Berndt, G. M. Tyce, and F. G. Knox
Chronic oral L-DOPA increases dopamine and decreases serotonin excretions
Am J Physiol Regulatory Integrative Comp Physiol, November 1, 1999; 277(5): R1476 - R1480.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
G. W. John, P. J. Pauwels, M. Perez, S. Halazy, B. Le Grand, Y. Verscheure, J.-P. Valentin, C. Palmier, T. Wurch, P. Chopin, et al.
F 11356, a Novel 5-Hydroxytryptamine (5-HT) Derivative with Potent, Selective, and Unique High Intrinsic Activity at 5-HT1B/1D Receptors in Models Relevant to Migraine
J. Pharmacol. Exp. Ther., July 1, 1999; 290(1): 83 - 95.
[Abstract] [Full Text]

Home page
 Mol. Endocrinol.Home page
P. M. C. Lembo, M. H. Ghahremani, and P. R. Albert
Receptor Selectivity of the Cloned Opossum G Protein-Coupled Receptor Kinase 2 (GRK2) in Intact Opossum Kidney Cells: Role in Desensitization of Endogenous {alpha}2C-Adrenergic but Not Serotonin 1B Receptors
Mol. Endocrinol., January 1, 1999; 13(1): 138 - 147.
[Abstract] [Full Text]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1992 by the American Society for Pharmacology and Experimental Therapeutics.