Endomorphin synthesis in rat brain from intracerebroventricularly injected [ 3H]-Tyr-Pro: A possible biosynthetic route for endomorphins

In spite of concentrated efforts, the biosynthetic route of μ-opioid receptor agonist brain tetrapeptide endomorphins (Tyr-Pro-Trp-Phe-NH 2 and Tyr-Pro-Phe-Phe-NH 2), discovered in 1997, is still obscure. We report presently that 30 min after intracerebroventricular injection of 20 or 200 μCi [ 3H]T...

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Bibliographic Details
Published in:Regulatory peptides 2006-03, Vol.134 (1), p.54-60
Main Authors: Rónai, András Z., Szemenyei, Erzsébet, Kató, Erzsébet, Kocsis, László, Orosz, György, Al-Khrasani, Mahmoud, Tóth, Géza
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Brain - metabolism
Chromatography, High Pressure Liquid
Dipeptides - metabolism
Dipeptides - pharmacology
Endomorphin de novo biosynthesis
Fundamental and applied biological sciences. Psychology
HPLC
Male
Motor Activity
Naloxone - metabolism
Naloxone - pharmacology
Oligopeptides - metabolism
Radiodetection
Rats
Rats, Wistar
Time Factors
Tritium - metabolism
Tyr-Pro substrate
Vertebrates: endocrinology
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Summary:In spite of concentrated efforts, the biosynthetic route of μ-opioid receptor agonist brain tetrapeptide endomorphins (Tyr-Pro-Trp-Phe-NH 2 and Tyr-Pro-Phe-Phe-NH 2), discovered in 1997, is still obscure. We report presently that 30 min after intracerebroventricular injection of 20 or 200 μCi [ 3H]Tyr-Pro (49.9 Ci mmol − 1 ) the incorporated radioactivity was found in endomorphin-related tetra- and tripeptides in rat brain extracts. As detected by the combination of HPLC with radiodetection, a peak corresponding to endomorphin-2-OH could be identified in two of four extracts of “20 μCi” series. Radioactive peaks in position of Tyr, Tyr-Pro, Tyr-Pro-Phe or Tyr-Pro-Trp appeared regularly in both series and also in the “tetrapeptide cluster” constituted by endomorphins and their free carboxylic forms. In one of the four extracts in the “200 μCi” series a robust active peak in the position of endomorphin 2 could be detected. Intracerebroventricularly injected 100 nmol, but not 10 or 1000 nmol cold Tyr-Pro (devoid of opioid activity in vitro), caused a naloxone-reversible prolongation of tail-flick latency in rats, peaking between 15 and 30 min. We suggest that Tyr-Pro may serve as a biosynthetic precursor to endomorphin synthesis.
ISSN:0167-0115
1873-1686
DOI:10.1016/j.regpep.2005.12.004