Galanin-5-hydroxytryptamine interactions: electrophysiological, immunohistochemical and in situ hybridization studies on rat dorsal raphe neurons with a note on galanin R1 and R2 receptors.
Galaninergic mechanisms related to 5-hydroxytryptamine neurons in the dorsal raphe nucleus of the rat were analysed using electrophysiology, immunohistochemistry and in situ hybridization. Galanin caused a dose-dependent hyperpolarization accompanied by a decrease in membrane resistance in most 5-hydroxytryptamine-sensitive dorsal raphe neurons. The galanin-induced outward current reversed at about - 105 mV and shifted to a more positive potential with increasing extracellular potassium concentrations. The 5-hydroxytryptamine-induced outward current was enhanced and prolonged by preincubation with a low concentration of galanin (1-10 nM). The immunohistochemical analysis showed (i) generally low levels of galanin in the 5-hydroxytryptamine cell bodies, (ii) moderate numbers of galanin-positive nerve endings around the 5-hydroxytryptamine cell bodies, (iii) presence of galanin-like immunoreactivity in 5-hydroxytryptamine-positive dendrites and (iv) galanin-positive, 5-hydroxytryptamine-negative boutons making synaptic contact with 5-hydroxytryptamine-positive dendrites. The in situ hybridization results suggest that the galanin receptor present in the galanin/5-hydroxytryptamine neurons is not of the recently cloned galanin-R1 type. Taken together these results indicate that galanin exerts an inhibitory effect via an increase in K+ conductance in 5-hydroxytryptamine neurons by acting on a postsynaptic receptor. In addition, galanin at low, possibly physiological concentrations enhances the inhibitory effect of 5-hydroxytryptamine at the cell soma level. We propose that galanin primarily is released from adjacent galanin boutons lacking 5-hydroxytryptamine and also from soma and dendrites of galanin/5-hydroxytryptamine dorsal raphe neurons. Galanin may thus be involved in the manifold functions hitherto ascribed to ascending 5-hydroxytryptamine neurons, for example in mood regulation.
Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
Z Q
ZQ
Xu
X
X
Zhang
V A
VA
Pieribone
S
S
Grillner
T
T
Hökfelt
D000818:Animals; D004553:Electric Conductivity; D005455:Fluorescent Antibody Technique; D019004:Galanin / Q000378:metabolism*; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials; D016253:Microscopy, Immunoelectron; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D011903:Raphe Nuclei / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044088:Receptors, Galanin; D018013:Receptors, Neuropeptide / Q000235:genetics / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
D012333:RNA, Messenger; D044088:Receptors, Galanin; D018013:Receptors, Neuropeptide; D012701:Serotonin; D013779:Tetrodotoxin; D019004:Galanin; D008274:Magnesium