Effects of galanin receptor agonists on locus coeruleus neurons.
Galanin exerts an inhibitory effect on locus coeruleus (LC) neurons via a postsynaptic, as yet unidentified galanin receptor. Using an in vitro intracellular recording technique the effect of two galanin receptor agonists on LC neurons was investigated. Bath application of [Sar(1), D-Ala(12)]gal(1-16)-NH(2) (AR-M961), an agonist both at galanin R1 and R2 (GALR1, GALR2) receptors, evoked a reversible membrane hyperpolarization and inhibition of spike discharge in all LC neurons tested (n=42). The action of AR-M961 was blocked by tetraethylammonium chloride. Hyperpolarizing responses induced by AR-M961 were retained in the presence of tetrodotoxin and high Mg(2+)/low Ca(2+) media. The selective GALR2 agonist Gal(2-11)-NH(2) (AR-M1896) only caused inhibition of spike discharge and a slight hyperpolarization in 26 of 34 LC neurons tested, and was on a molar basis much weaker than AR-M961. These results suggest that it mainly is the GALR1 receptor that mediates hyperpolarization of LC neurons.
Ma
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Department of Neuroscience, Karolinska Institutet, Berzelius Vag 1, S-171 77, Stockholm, Sweden.
Tong
Y G
YG
Schmidt
R
R
Brown
W
W
Payza
K
K
Hodzic
L
L
Pou
C
C
Godbout
C
C
Hökfelt
T
T
Xu
Z Q
ZQ
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D019004:Galanin / Q000378:metabolism* / Q000494:pharmacology; D008125:Locus Coeruleus / Q000166:cytology / Q000187:drug effects*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044088:Receptors, Galanin; D018013:Receptors, Neuropeptide / Q000819:agonists* / Q000502:physiology
D044088:Receptors, Galanin; D018013:Receptors, Neuropeptide; D019004:Galanin