Biomaterial Database

Tryptophan hydroxylase inhibition increases preprotachykinin mRNA in developing and adult medullary raphe nuclei. 1990

P D Walker, and S Schotland, and R P Hart, and G M Jonakait

Department of Biological Sciences, Rutgers University, Newark, NJ 07102.

In order to study the regulation of co-localized monoamine and peptide neurotransmitters in the medullary raphe nuclei (MRN), we determined whether inhibition of serotonin (5-HT) synthesis affected levels of preprotachykinin (PPT; the prohormone precursor of substance P) mRNA in the MRN. Adult rats received p-chlorophenylalanine (pCPA), an irreversible inhibitor of tryptophan hydroxylase (TPH), via Alzet minipumps. TPH activity was inhibited by 70-80% for 3 weeks following pump implantation. During this period Northern mRNA analysis revealed that PPT mRNA levels in the MRN were increased 1.5-2-fold. The pCPA-induced increase was specific for PPT mRNA since no change was detected in mRNA coding for neuron-specific enolase (NSE; a constitutive neuronal protein) or 28 S ribosomal RNA. To determine whether fetal inhibition of 5-HT synthesis affected development of PPT mRNA in the MRN, pregnant rats were administered pCPA via Alzet minipump implanted on embryonic day 8. In pCPA-treated litters TPH activity was decreased by 60-70% from E16 to postnatal day 3 (P3), returning to control levels by P8. Northern mRNA analysis revealed that PPT mRNA levels increased 2.4-fold of control levels at P1. Infusion of pCPA for one week resulted in an earlier increase in PPT mRNA levels, suggesting that birth was not required to elicit the surge in PPT message. These results support the hypothesis that alterations in 5-HT metabolism have regulatory consequences for co-localized substance P formation in the MRN.

UI	MeSH Term	Description	Entries
D007262	Infusions, Intravenous	The long-term (minutes to hours) administration of a fluid into the vein through venipuncture, either by letting the fluid flow by gravity or by pumping it.	Drip Infusions,Intravenous Drip,Intravenous Infusions,Drip Infusion,Drip, Intravenous,Infusion, Drip,Infusion, Intravenous,Infusions, Drip,Intravenous Infusion
D007279	Injections, Subcutaneous	Forceful administration under the skin of liquid medication, nutrient, or other fluid through a hollow needle piercing the skin.	Subcutaneous Injections,Injection, Subcutaneous,Subcutaneous Injection
D010134	Fenclonine	A selective and irreversible inhibitor of tryptophan hydroxylase, a rate-limiting enzyme in the biosynthesis of serotonin (5-HYDROXYTRYPTAMINE). Fenclonine acts pharmacologically to deplete endogenous levels of serotonin.	p-Chlorophenylalanine,para-Chlorophenylalanine,CP-10,188,DL-3-(4-Chlorophenyl)alanine,Fenclonin,Fenclonine (L)-Isomer,Fenclonine Hydrobromide,Fenclonine Hydrochloride,Fenclonine, (D)-Isomer,Hydrobromide, Fenclonine,Hydrochloride, Fenclonine,para Chlorophenylalanine
D011498	Protein Precursors		Precursors, Protein
D011903	Raphe Nuclei	Collections of small neurons centrally scattered among many fibers from the level of the TROCHLEAR NUCLEUS in the midbrain to the hypoglossal area in the MEDULLA OBLONGATA.	Caudal Linear Nucleus of the Raphe,Interfascicular Nucleus,Nucleus Incertus,Rostral Linear Nucleus of Raphe,Rostral Linear Nucleus of the Raphe,Superior Central Nucleus,Central Nucleus, Superior,Incertus, Nucleus,Nuclei, Raphe,Nucleus, Interfascicular,Nucleus, Raphe,Nucleus, Superior Central,Raphe Nucleus
D011919	Rats, Inbred Strains	Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.	August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D005260	Female		Females
D005786	Gene Expression Regulation	Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.	Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000831	Animals, Newborn	Refers to animals in the period of time just after birth.	Animals, Neonatal,Animal, Neonatal,Animal, Newborn,Neonatal Animal,Neonatal Animals,Newborn Animal,Newborn Animals