M-15: high-affinity chimeric peptide that blocks the neuronal actions of galanin in the hippocampus, locus coeruleus, and spinal cord.
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.
Bartfai
T
T
Department of Biochemistry, Arrheniuslaboratories, Stockholm University, Sweden.
Bedecs
K
K
Land
T
T
Langel
U
U
Bertorelli
R
R
Girotti
P
P
Consolo
S
S
Xu
X J
XJ
Wiesenfeld-Hallin
Z
Z
Nilsson
S
S
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism; D002678:Chimera; D004553:Electric Conductivity / Q000187:drug effects; D019004:Galanin / Q000031:analogs & derivatives; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D007700:Kinetics; D008125:Locus Coeruleus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009479:Neuropeptides / Q000494:pharmacology*; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D044088:Receptors, Galanin; D011964:Receptors, Gastrointestinal Hormone / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013373:Substance P / Q000031:analogs & derivatives*
D007457:Iodine Radioisotopes; D009479:Neuropeptides; D010455:Peptides; D044088:Receptors, Galanin; D011964:Receptors, Gastrointestinal Hormone; C074975:galantide; D013373:Substance P; D019004:Galanin; D000109:Acetylcholine