Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Substance P (SP) and thyrotrophin-releasing hormone (TRH) are co-localized with serotonin (5-HT) in cells of the medullary raphe nuclei. In order to examine the factors that control development of multiple neurotransmitters within individual brain nuclei, we have grown presumptive raphe nuclei in organotypic tissue culture, an environment in which mammalian embryonic brain is easily accessible and manipulable. Tissue was obtained from E13 mice. A discrete midline segment of the rhombencephalon was dissected intact or was separated into 'rostral' (RR) and 'medullary' (MR) fragments. Tissue was explanted onto collagen coverslips and grown for up to two weeks in Maximow depression chambers. Tryptophan hydroxylase (TPH), the rate-limiting enzyme in 5-HT biosynthesis, was barely detectable at explantation. During the first week in culture, however, TPH activity increased 7-fold. After two weeks, TPH activity increased almost 2.5-fold above the one-week level. Immunocytochemical analysis of the cultures confirmed a widespread distribution of 5-HT-positive cells and fibers throughout the explant. SP, monitored by radioimmunoassay, was detected after two days in culture, and attained a level of 111.7 +/- 9.8 pg/culture after two weeks. TRH activity was similarly elevated after two weeks in vitro. Therefore, developmental increases in TPH, SP, and TRH occurred in culture, mimicking the condition in vivo. RR and MR fragments, when grown apart on separate coverslips, developed 1.57-2.26 times the TPH activity that developed in the undivided piece. Inclusion of 1 microM pargyline in the fragments restored TPH to control levels. The effect of pargyline was blocked by methiothepin, suggesting autoreceptor-mediated regulation.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Development of serotonin, substance P and thyrotrophin-releasing hormone in mouse medullary raphe grown in organotypic tissue culture: developmental regulation by serotonin. 246 25

Family studies have provided evidence for familial transmission in suicide in major psychiatric disorders, and in particular affective disorders. Even though they may seem contradictory, linkage studies have suggested several genetic regions implicated in affective disorders. Association studies have mainly focused on genes related to serotonergic and monoaminergic pathways. Other genes involved in GABAergic and substance P pathways have also been studied in association studies. Another way to approach the genetics of affective disorders is the definition of more detailed phenotypes. Suicidal behaviour is one of the more largely studied subphenotypes within affective disorders. Tryptophan hydroxylase and serotonin transporter genes, related to the serotonergic pathway, have been found to be associated to suicidal behaviour, in particular violent suicidal behaviour but need to be replicated before definitive conclusion. Improved methodologies and updated tools in genetic studies will improve in the future our knowledge of affective disorders.
 ...
PMID:Molecular genetics of affective disorders. 1289 Mar 9