Abstract
The guinea pig ileum possesses NK-1 and NK-3 tachykinin receptors. As expected, [Pro9]SP and senktide, which are selective agonists of NK-1 and NK-3 receptors, respectively, were found to be highly potent in contracting the guinea pig ileum. Surprisingly, similar observations were made with septide, SP-O-CH3, [Apa9-10]SP, or [Pro9,10]SP although, in contrast to [Pro9]SP, these four peptides showed a low affinity for 3H-[Pro9]SP-specific NK-1 binding sites on membranes from the guinea pig ileum. They were also devoid of affinity for NK-2 and NK-3 binding sites. GR 71251, a compound which has been described as a NK-1 antagonist, was more potent in inhibiting the septide- than the [Pro9]SP-evoked contracting response. Altogether, these results suggest that septide, [Apa9-10]SP, and [Pro9,10]SP exert their high contracting activity in the guinea pig ileum by acting on a new subtype of tachykinin receptors.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Binding, Competitive
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Cell Membrane / drug effects
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Dose-Response Relationship, Drug
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Eledoisin / analogs & derivatives
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Eledoisin / metabolism
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Guinea Pigs
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Ileum / chemistry*
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Ileum / drug effects
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Indicators and Reagents
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Inositol / metabolism
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Iodine Radioisotopes
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Muscle Contraction / drug effects
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Parotid Gland / drug effects
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Parotid Gland / metabolism
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Peptide Fragments / pharmacology
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Rats
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Rats, Inbred Strains
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Receptors, Neurotransmitter / analysis*
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Receptors, Neurotransmitter / drug effects
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Receptors, Tachykinin
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Substance P / analogs & derivatives
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Substance P / pharmacology
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Succinimides / metabolism
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Tachykinins / metabolism*
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Tachykinins / pharmacology
Substances
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Bolton Hunter-eledoisin ligand
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Indicators and Reagents
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Iodine Radioisotopes
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Peptide Fragments
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Receptors, Neurotransmitter
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Receptors, Tachykinin
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Succinimides
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Tachykinins
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Substance P
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Inositol
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Eledoisin