Highly selective agonists for substance P receptor subtypes.

U. Wormser*, R. Laufer, Y. Hart, M. Chorev, C. Gilon, Z. Selinger

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

288 Scopus citations

Abstract

The existence of a third tachykinin receptor (SP-N) in the mammalian nervous system was demonstrated by development of highly selective agonists. Systematic N-methylation of individual peptide bonds in the C-terminal hexapeptide of substance P gave rise to agonists which specifically act on different receptor subtypes. The most selective analog of this series, succinyl-[Asp6,Me-Phe8]SP6-11, elicits half-maximal contraction of the guinea pig ileum through the neuronal SP-N receptor at a concentration of 0.5 nM. At least 60,000-fold higher concentrations of this peptide are required to stimulate the other two tachykinin receptors (SP-P and SP-E). The action of selective SP-N agonists in the guinea pig ileum is antagonized by opioid peptides, suggesting a functional counteraction between opiate and SP-N receptors. These results indicate that the tachykinin receptors are distinct entities which may mediate different physiological functions.

Original languageEnglish
Pages (from-to)2805-2808
Number of pages4
JournalEMBO Journal
Volume5
Issue number11
DOIs
StatePublished - Nov 1986

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