ATTENTION: The software behind KU ScholarWorks is being upgraded to a new version. Starting July 15th, users will not be able to log in to the system, add items, nor make any changes until the new version is in place at the end of July. Searching for articles and opening files will continue to work while the system is being updated.
If you have any questions, please contact Marianne Reed at mreed@ku.edu .
Characterization of the functional heterologous desensitization of hypothalamic 5-HT1A receptors after 5-HT2A receptor activation
dc.contributor.author | Zhang, Yahong | |
dc.contributor.author | D'Souza, Deborah N. | |
dc.contributor.author | Raap, Danı́ K. | |
dc.contributor.author | Garcia, Francisca | |
dc.contributor.author | Battaglia, George | |
dc.contributor.author | Muma, Nancy A. | |
dc.contributor.author | Van de Kar, Louis D. | |
dc.date.accessioned | 2015-05-11T17:25:21Z | |
dc.date.available | 2015-05-11T17:25:21Z | |
dc.date.issued | 2001-10-15 | |
dc.identifier.citation | Zhang, Y., D'Souza, D., Raap, D. K., Garcia, F., et al. (2001) Characterization of the functional heterologous desensitization of hypothalamic 5-HT1A receptors after 5-HT2A receptor activation. J. Neurosci, 21(20), 7919-7927. | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/17696 | |
dc.description | This is the publisher's version, also available electronically from "www.jneurosci.org". | en_US |
dc.description.abstract | Desensitization of 5-HT1A receptors could be involved in the long-term therapeutic effect of anxiolytic and antidepressant drugs. Pretreatment of rats with the 5-HT2A/2C agonist DOI induces an attenuation of hypothalamic 5-HT1Areceptor–Gz-protein signaling, measured as the ACTH and oxytocin responses to an injection of the 5-HT1A agonist 8-OH-DPAT. We characterized this functional heterologous desensitization of 5-HT1A receptors in rats and examined some of the mechanisms that are involved. A time course experiment revealed that DOI produces a delayed and reversible reduction of the ACTH and oxytocin responses to an 8-OH-DPAT challenge. The maximal desensitization occurred at 2 hr, and it disappeared 24 hr after DOI injection. The desensitization was dose-dependent, and it shifted the oxytocin and ACTH dose–response curves of 8-OH-DPAT to the right (increased ED50) with no change in their maximal responses (E max). The 5-HT2A receptor antagonist MDL 100,907 prevented the DOI-induced desensitization, indicating that 5-HT2Areceptors mediate the effect of DOI. Analysis of the components of the 5-HT1A receptor–Gz-protein signaling system showed that DOI did not alter the level of membrane-associated Gz-proteins in the hypothalamus. Additionally, DOI did not alter the binding of [3H]8-OH-DPAT or the inhibition by GTPγS of [3H]8-OH-DPAT binding in the hypothalamus. In conclusion, the activation of 5-HT2Areceptors induces a transient functional desensitization of 5-HT1A receptor signaling in the hypothalamus, which may occur distal to the 5-HT1A receptor–Gz-protein interface. | en_US |
dc.publisher | Society for Neuroscience | en_US |
dc.relation.isversionof | http://www.jneurosci.org/content/21/20/7919 | en_US |
dc.title | Characterization of the functional heterologous desensitization of hypothalamic 5-HT1A receptors after 5-HT2A receptor activation | en_US |
dc.type | Article | |
kusw.kuauthor | Muma, Nancy A. | |
kusw.kudepartment | Pharmacology & Toxicology | en_US |
kusw.oaversion | Scholarly/refereed, publisher version | |
kusw.oapolicy | This item does not meet KU Open Access policy criteria. | |
dc.rights.accessrights | openAccess |
Files in this item
This item appears in the following Collection(s)
-
Pharmacy Scholarly Works [299]