Serotonin modulates the levels of mRNAS coding for thyrotropin-releasing hormone and preprotachykinin by different mechanisms in medullary raphe neurons.
The serotonergic neurons of the medullary raphe also contain the peptide neurotransmitters substance P (SP) and thyrotropin releasing hormone (TRH). In this study we asked whether the manipulation of serotonin levels alters the levels of mRNA coding for pre-proTRH. Just like the mRNA coding for the precursor of SP (preprotachykinin, PPT), levels of TRH mRNA are increased when serotonin synthesis is inhibited by para-chlorophenylalanine (pCPA) and decreased when serotonin reuptake is blocked by zimelidine. However, subtle differences suggest that the mechanisms behind these changes are different. Levels of TRH mRNA are still decreased after 14 days of zimelidine treatment, a time when levels of PPT mRNA have returned to control values. In addition, the serotonin reuptake blocker fluoxetine lowers levels of TRH but not PPT mRNA. Finally, the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) induces a transient decrease in levels of PPT mRNA similar to that induced by zimelidine, but does not decrease levels of TRH mRNA even when 10-fold higher doses are administered. These results suggest that while some pharmacological manipulations appear to alter TRH and PPT mRNA levels coordinately, the mechanisms regulating the synthesis of these two colocalized neurotransmitters are different.
Department of Biological Sciences, Rutgers University, Newark, NJ 07102.
L A
LA
Riley
G M
GM
Jonakait
R P
RP
Hart
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D005815:Genetic Code; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics*; D015347:RNA Probes; D012333:RNA, Messenger / Q000378:metabolism*; D011903:Raphe Nuclei / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects; D015320:Tachykinins / Q000235:genetics*; D013973:Thyrotropin-Releasing Hormone / Q000235:genetics*; D015031:Zimeldine / Q000494:pharmacology
D011498:Protein Precursors; D015347:RNA Probes; D012333:RNA, Messenger; D015320:Tachykinins; C044206:preprotachykinin; D012701:Serotonin; D015031:Zimeldine; D013973:Thyrotropin-Releasing Hormone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin