The posterior pituitary expresses the serotonin receptor 2C.

Autor: Welden JR; Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, KY, 40503, United States., Zhang Z; Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, KY, 40503, United States., Duncan MJ; Dept. of Neuroscience, University of Kentucky College of Medicine, Lexington, KY, 40536, United States., Falaleeva M; Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, KY, 40503, United States., Wells T; School of Biosciences, Cardiff University, Cardiff, CF10 3AX, United Kingdom., Stamm S; Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, KY, 40503, United States. Electronic address: Stefan@stamms-lab.net.
Jazyk: angličtina
Zdroj: Neuroscience letters [Neurosci Lett] 2018 Sep 25; Vol. 684, pp. 132-139. Date of Electronic Publication: 2018 Jun 30.
DOI: 10.1016/j.neulet.2018.06.051
Abstrakt: The serotonin receptor 2C (5HT2C) is an important drug target to treat obesity and depression. Its pre-mRNA undergoes alternative splicing, encoding a short RNA1 isoform that is localized intracellularly and a full-length isoform (RNA2) that can reach the cell membrane. These splicing isoforms are deregulated in Prader-Willi syndrome (PWS), due to the loss of a trans-acting regulatory RNA, SNORD115. Here we show that the 5HT2C mRNA is expressed in the posterior pituitary, suggesting that 5HT2C mRNA is generated in the hypothalamus and subsequently conveyed by axonal transport. In the pituitary, the ratio of 5HT2C isoforms is regulated by feeding, and can be manipulated using a splice-site changing oligonucleotide injected into the blood. The pituitary expression of the 5HT2C mRNA may constitute a previously unknown mechanism whereby serotonin in the circulation or drugs targeting the 5HT2C might induce side-effects. Finally, the deregulation of 5HT2C splicing isoforms in PWS could contribute to the known hormonal imbalances.
(Copyright © 2018. Published by Elsevier B.V.)
Databáze: MEDLINE
Externí odkaz: