Linked Life Data

11958869

Source:http://linkedlifedata.com/resource/pubmed/id/11958869

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2002-4-17
pubmed:abstractText
Neurons expressing the preprotachykinin A gene, which encodes the sequences of substance P, neurokinin A, neuropeptide gamma and neuropeptide K, exemplify peptide co-existence. Furthermore, there is also evidence that substance P fragments have biological activity. However, the relative contribution of each of these peptides to tachykinin signalling is still poorly understood. An important factor which will determine the characteristics of the signal mediated by co-localised peptides is their clearance from the extracellular space. The striatum, in which tachykinins are present and exert neuromodulatory roles, can be used as a model to investigate this aspect. Therefore, in this study we characterised in vivo in the striatum the metabolism and clearance of substance P and of the other three co-expressed peptides. After intrastriatal administration of 1 pmol, tritiated substance P disappeared too rapidly for metabolites to be detected. However, when 10 nmol substance P and 1 pmol tritiated substance P were co-injected, substance P(1-4) and substance P(1-7), which are biologically active, were detected as major metabolites. Under these conditions, the rate of decay of tritiated substance P was 0.2 nmol/min. The effects of the peptidase inhibitors thiorphan, bestatin and captopril suggested that neutral endopeptidase 24.11 and aminopeptidases were involved in primary substance P cleavages, whereas angiotensin-converting enzyme was involved in secondary cleavages. The monitoring of the decay of unlabelled substance P by high-performance liquid chromatography gave a rate of 0.16 nmol/min. Using high-performance liquid chromatography with capillary electrophoresis, the rates of decay of 10 nmol neurokinin A or neuropeptide gamma were five and seven times faster than that of substance P. In contrast, over the time course of the experiment, no significant decay of neuropeptide K was detected. These results show that substance P disappears rapidly from the extracellular space, and supports the formation in vivo of major N-terminal active substance P metabolites. Our study also highlights significant differences in the clearance of co-expressed tachykinins and suggests that certain species may disappear relatively slowly from the extracellular space, and thus may make a significant temporal and spatial contribution to signalling.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0306-4522
pubmed:author
pubmed:issnType
Print
pubmed:volume
110
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
277-86
pubmed:dateRevised
2005-5-14
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
In vivo metabolism and clearance of substance P and co-expressed tachykinins in rat striatum.
pubmed:affiliation
Neuroscience Section, Division of Biomedical Sciences, St. Bartholowmew's and the Royal London School of Medicine and Dentistry, Queen Mary and Westfield College, London, UK. a.t.michael-titus@qmw.ac.uk
pubmed:publicationType
Journal Article