Dynorphin block of N-methyl-D-aspartate channels increases with the peptide length

Li Chen, Li-Yen Huang

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

We examined the non-opioid actions of various forms of dynorphin A (DynA) on N-methyI-D-aspartate (NMDA) receptor channels in isolated rat trigeminal neurons using the whole-cell patch recording technique. All the dynorphins tested blocked NMDA-activated currents. The blocking actions were voltage-independent. The IC50 was 0.26 μM for DynA(1-32), 6.6 μM for DynA(1-17) 7.4 μM for DynA(1-13), 42.0 μM for DynA(1-10). DynA(1-8) had no detectable blocking action on NMDA responses. Thus, the IC50s of dynorphins for NMDA receptors increased 160-fold as the length of the peptides decreased from 32 to 10 amino acids. Amidation of dynorphins dramatically reduced their IC50s and eliminated the large difference in the IC50s of various lengths of dynorphins. The reduction in the IC50s of dynorphin amides could not be explained by the resistance of the peptides to enzymatic degradation. Our observations suggest that peptide processing affects dynorphin blocking actions on NMDA responses. The positively charged residues, lengths of the peptides and amidation may contribute to their affinities for NMDA receptors.

Original languageEnglish (US)
Pages (from-to)826-831
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume284
Issue number3
StatePublished - Mar 1998
Externally publishedYes

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Dynorphins
N-Methylaspartate
D-Aspartic Acid
Peptides
dynorphin (1-8)
Patch-Clamp Techniques
Amides
Inhibitory Concentration 50
Neurons
Amino Acids

ASJC Scopus subject areas

  • Pharmacology

Cite this

Dynorphin block of N-methyl-D-aspartate channels increases with the peptide length. / Chen, Li; Huang, Li-Yen.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 284, No. 3, 03.1998, p. 826-831.

Research output: Contribution to journalArticle

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