The 5HT5A serotonin receptor is expressed predominantly by astrocytes in which it inhibits cAMP accumulation: a mechanism for neuronal suppression of reactive astrocytes.
The mRNA for the 5-hydroxytryptamine receptor 5-HT5A was detected at embryonic day 18 in the rat central nervous system and peaked by postnatal day 20. At all time points examined, 5-HT5A immunoreactivity observed on astrocyte cell bodies and in the stellate processes not only colocalized with the astrocyte-specific marker glial fibrillary acidic protein (GFAP) but was coordinately regulated with GFAP, increasing during development and during gliosis. Transfection of 5-HT5A into glioma cells prevented the 5-HT-induced increase in cAMP observed in untransfected cells and decreased the relative forskolin response by approximately 20%, suggesting that the 5-HT5A receptor couples negatively to adenylyl cyclase in astrocytes. Together, these results indicate a neuron-to-astrocyte serotonergic signaling pathway mediating cAMP concentrations, which could provide a neuronally driven mechanism for regulating astrocyte physiology with relevance to gliosis.
Carson
M J
MJ
Department of Molecular Biology, Scripps Research Institute, La Jolla, California 92037, USA.
Thomas
E A
EA
Danielson
P E
PE
Sutcliffe
J G
JG
D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism* / Q000502:physiology; D000242:Cyclic AMP / Q000037:antagonists & inhibitors*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011985:Receptors, Serotonin / Q000235:genetics / Q000378:metabolism*
D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger; D011985:Receptors, Serotonin; D000242:Cyclic AMP