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

A. Rónai, Erzsébet Szemenyei, Erzsébet Kató, László Kocsis, G. Orosz, M. Al-Khrasani, Géza Tóth

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

In spite of concentrated efforts, the biosynthetic route of μ-opioid receptor agonist brain tetrapeptide endomorphins (Tyr-Pro-Trp-Phe-NH2 and Tyr-Pro-Phe-Phe-NH2), 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.

Original languageEnglish
Pages (from-to)54-60
Number of pages7
JournalRegulatory Peptides
Volume134
Issue number1
DOIs
Publication statusPublished - Mar 15 2006

Fingerprint

tyrosyl-proline
Rats
Brain
Radioactivity
Opioid Receptors
Naloxone
Opioid Analgesics
Tail
High Pressure Liquid Chromatography
Injections
endomorphin 2

Keywords

  • Endomorphin de novo biosynthesis
  • HPLC
  • Radiodetection
  • Tyr-Pro substrate

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology
  • Neuroscience(all)

Cite this

Endomorphin synthesis in rat brain from intracerebroventricularly injected [3H]-Tyr-Pro : A possible biosynthetic route for endomorphins. / Rónai, A.; Szemenyei, Erzsébet; Kató, Erzsébet; Kocsis, László; Orosz, G.; Al-Khrasani, M.; Tóth, Géza.

In: Regulatory Peptides, Vol. 134, No. 1, 15.03.2006, p. 54-60.

Research output: Contribution to journalArticle

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AU - Kató, Erzsébet

AU - Kocsis, László

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AB - In spite of concentrated efforts, the biosynthetic route of μ-opioid receptor agonist brain tetrapeptide endomorphins (Tyr-Pro-Trp-Phe-NH2 and Tyr-Pro-Phe-Phe-NH2), 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.

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