galanin-(1-15) and galanin-(1-16)

The effects of the 29-amino acid neuropeptide galanin [GAL (1-29)], GAL(1-15), GAL(1-16), and the GAL subtype 2 receptor agonist D-tryptophan(2)-GAL(1-29) were studied in the dorsal hippocampus in vitro with intracellular recording techniques. GAL(1-15) induced, in the presence of tetrodotoxin, a dose-dependent hyperpolarization in hippocampal CA3 neurons. Most of the GAL(1-15)-sensitive neurons did not respond to GAL(1-29), GAL(1-16), or D-tryptophan(2)-GAL(1-29). These results indicate the presence of a distinct, yet-to-be cloned GAL(1-15)-selective receptor on CA3 neurons in the dorsal hippocampus.

Topics: Animals; Galanin; Hippocampus; Male; Membrane Potentials; Peptide Fragments; Rats; Rats, Sprague-Dawley; Receptors, Galanin; Receptors, Neuropeptide

It is thought that galanin, a 29 amino acid neuropeptide, is involved in various neuronal functions, including the regulation of food intake and hormone release. Consistent with this idea, galanin receptors have been demonstrated throughout the brain, with high levels being observed in the hypothalamus. However, little is known about the mechanisms by which galanin elicits its actions in the brain. Therefore, we studied the effects of galanin and its analogs on synaptic transmission using an in vitro slice preparation of rat hypothalamus. In arcuate nucleus neurons, application of galanin resulted in an inhibition of evoked glutamatergic EPSCs and a decrease in paired-pulse depression, indicating a presynaptic action. The fragments galanin 1-16 and 1-15 produced a robust depression of synaptic transmission, whereas the fragment 3-29 produced a lesser degree of depression. The chimeric peptides C7, M15, M32, and M40, which have been reported to antagonize some actions of galanin, all produced varying degrees of depression of evoked EPSCs. In a minority of cases, C7, M15, and M40 antagonized the actions of galanin. Analysis of mEPSCs in the presence of TTX and Cd2+, or after application of alpha-latrotoxin, indicated a site of action for galanin downstream of Ca2+ entry. Thus, our data suggest that galanin acts via several subtypes of presynaptic receptors to depress synaptic transmission in the rat arcuate nucleus.

Topics: alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Animals; Arcuate Nucleus of Hypothalamus; Complement C7; Excitatory Amino Acid Agonists; Female; Galanin; Glutamic Acid; GTP-Binding Proteins; Male; Neural Inhibition; Neuropeptides; Patch-Clamp Techniques; Peptide Fragments; Rats; Rats, Wistar; Receptors, AMPA; Receptors, Galanin; Receptors, Gastrointestinal Hormone; Spider Venoms; Substance P; Synaptic Transmission