Direct inhibitory action of galanin on hypothalamic arcuate nucleus neurones expressing galanin receptor Gal-r1 mRNA.
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.
Poulain
Pierre
P
INSERM U.422, Lille, France. poulain@lille.inserm.fr
Decrocq
Noëlle
N
Mitchell
Valérie
V
D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D004553:Electric Conductivity; D004594:Electrophysiology; D019004:Galanin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D008239:Lysine / Q000031:analogs & derivatives* / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials; D009433:Neural Inhibition / Q000187:drug effects; D009474:Neurons / Q000145:classification / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044088:Receptors, Galanin; D018013:Receptors, Neuropeptide / Q000235:genetics / Q000378:metabolism*; D013373:Substance P / Q000031:analogs & derivatives* / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D000779:Anesthetics, Local; D012333:RNA, Messenger; D044088:Receptors, Galanin; D018013:Receptors, Neuropeptide; C074975:galantide; D013373:Substance P; D013779:Tetrodotoxin; D019004:Galanin; C013411:biocytin; D008239:Lysine