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Highly selective agonists for substance P receptor subtypes.

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

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AcetylcholineAnimalsAtropineGuinea PigsIleumIn Vitro TechniquesMuscle ContractionMuscle, SmoothNerve Tissue ProteinsNeuropeptidesReceptors, Neurokinin-1Receptors, NeurotransmitterReceptors, TachykininSubstance PTachykininsJournal Article

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BibTeXRIS

U Wormser, R Laufer, Y Hart, M Chorev, C Gilon, Z Selinger. 1986. Highly selective agonists for substance P receptor subtypes.. https://doi.org/10.1002/j.1460-2075.1986.tb04571.x

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