Direct inhibitory action of galanin on hypothalamic arcuate nucleus neurones expressing galanin receptor Gal-r1 mRNA

Neuroendocrinology. 2003 Aug;78(2):105-17. doi: 10.1159/000071966.

Abstract

Galanin may act in the regulation of reproduction and feeding behaviour through a direct action on arcuate nucleus (ARC) neurones but evidence for a postsynaptic action is absent. The effects of rat galanin(1-29) on rat ARC neurones were examined during recordings with biocytin-filled sharp microelectrodes from brain slices. Neurones were subsequently visualised and hybridized for the mRNA of the galanin receptor Gal-R1. Current-clamp recordings revealed that ARC neurones displayed a functional heterogeneity in their firing properties. A great majority of neurones showed low-threshold spikes, instantaneous and time-dependent inward rectifications and an outward rectification. Two types of bursting behaviours were recorded, depending on the level of the membrane potential. Galanin (500 nM) elicited a reversible hyperpolarisation with a decrease in the resistance or a decrease in resistance only in 9 of 34 tested neurones, independent of the electrophysiological phenotype. The reversal potential for the galanin response was about -94 mV, near the equilibrium potential for K(+). Galantide (10 nM) antagonised the effects which were not blocked by tetrodotoxin, indicating a postsynaptic action. In situ hybridisation revealed that Gal-R1 mRNA occurred in the neurones that responded to galanin, whereas the unresponsive neurones never exhibited the hybridisation signal. This suggests that the responsive neurones possess functional postsynaptic Gal-R1. The study demonstrates for the first time a direct inhibitory action of galanin on ARC neurones, probably mediated by activation of Gal-R1. This action may have important implications for the functioning of neurones involved in the regulation of reproduction and feeding behaviour, such as proopiomelanocortin neurones.

Publication types

  • Comparative Study

MeSH terms

  • Anesthetics, Local / pharmacology
  • Animals
  • Arcuate Nucleus of Hypothalamus / drug effects*
  • Arcuate Nucleus of Hypothalamus / metabolism
  • Electric Conductivity
  • Electrophysiology
  • Galanin / analogs & derivatives*
  • Galanin / pharmacology*
  • Gene Expression / drug effects
  • In Situ Hybridization
  • In Vitro Techniques
  • Lysine / analogs & derivatives*
  • Lysine / metabolism
  • Male
  • Membrane Potentials
  • Neural Inhibition / drug effects
  • Neurons / classification
  • Neurons / drug effects*
  • Neurons / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, Galanin
  • Receptors, Neuropeptide / genetics
  • Receptors, Neuropeptide / metabolism*
  • Substance P / analogs & derivatives*
  • Substance P / pharmacology
  • Tetrodotoxin / pharmacology

Substances

  • Anesthetics, Local
  • RNA, Messenger
  • Receptors, Galanin
  • Receptors, Neuropeptide
  • galantide
  • Substance P
  • Tetrodotoxin
  • Galanin
  • biocytin
  • Lysine