Abstract
The 20-amino acid peptide M-15 binds with high affinity (IC50 approximately 0.1 nM) to 125I-labeled galanin (125I-GAL) binding sites in membranes from the ventral hippocampus, midbrain, and rat spinal cord. Receptor autoradiographic studies show that M-15 can displace 125I-GAL from all labeled sites. M-15 acts as a reversible high-affinity antagonist in blocking the inhibitory effects of GAL on the evoked release of acetylcholine in vivo in the hippocampus and on the GAL-induced hyperpolarization of locus coeruleus neurons in slices. M-15 also blocks the facilitatory effects of GAL on the spinal flexor reflex. Thus, the chimeric peptide M-15 [GAL-(1-13)-substance P-(5-11)amide] represents the first antagonist to the neuronal actions of GAL.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acetylcholine / pharmacology
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Animals
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Autoradiography
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Binding Sites
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Binding, Competitive
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Cell Membrane / metabolism
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Chimera
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Electric Conductivity / drug effects
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Galanin
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Hippocampus / drug effects
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Hippocampus / physiology*
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In Vitro Techniques
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Iodine Radioisotopes
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Kinetics
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Locus Coeruleus / drug effects
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Locus Coeruleus / physiology*
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Male
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Membrane Potentials / drug effects
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Neurons / drug effects
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Neurons / physiology*
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Neuropeptides / pharmacology*
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Peptides / chemical synthesis
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Peptides / metabolism
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Peptides / pharmacology*
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Rats
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Rats, Inbred Strains
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Receptors, Galanin
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Receptors, Gastrointestinal Hormone / drug effects
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Receptors, Gastrointestinal Hormone / physiology*
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Spinal Cord / drug effects
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Spinal Cord / physiology*
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Substance P* / analogs & derivatives*
Substances
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Iodine Radioisotopes
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Neuropeptides
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Peptides
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Receptors, Galanin
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Receptors, Gastrointestinal Hormone
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galantide
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Substance P
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Galanin
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Acetylcholine