Distribution and differential regulation of galanin receptor subtypes in rat brain: effects of seizure activity.
Galanin, acting at the GalR1-3 subtypes of galanin receptors, is involved in the regulation of cognition, mood, feeding, seizure activity and pain. The understanding of galanin's effects in molecular and cellular terms has been hampered by the lack of receptor subtype selective ligands and antibodies. Previous in situ hybridization data showed that GalR1 and GalR2 receptors are abundant in the rat brain, while the distribution of GalR3 is contradictory and most studies demonstrated a low expression levels in the rat brain. The distribution of galanin receptor subtypes at protein level is unknown. In the present study, we report the regional distribution of the galanin receptors: GalR1 and non-GalR1 receptors, using a recently synthesized high affinity GalR2/3 selective ligand, galanin (2-11), and galanin (1-29), as competitors, in saturating (125)I-galanin membrane binding assay. We show that paraventricular nucleus (PVN) express predominantly GalR1, whereas areas like the dorsal raphe nucleus (DRN), hippocampus and amygdala express both the GalR1 and non-GalR1 receptors. We speculate that the GalR2/3 binding sites detected by galanin (2-11) binding in our study probably represent mostly GalR2 receptors. In addition, we show regionally specific and subtype specific regulation of galanin receptors. Status epilepticus (SE), known to deplete galanin from axonal projections of locus coeruleus and septum/diagonal band neurons in the hippocampus and to induce galanin expression in a subset of hippocampal cells, down regulates GalR2 receptor mRNA and proteins by 30% without altering the GalR1 receptors.
Lu
Xiaoying
X
Department of Neuropharmacology, The Harold L. Dorris Neurological Research Center, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Mazarati
Andrey
A
Sanna
Pietro
P
Shinmei
Steve
S
Bartfai
Tamas
T
D000679:Amygdala / Q000502:physiology; D000818:Animals; D001921:Brain / Q000502:physiology*; D016466:CHO Cells; D006224:Cricetinae; D015536:Down-Regulation; D019004:Galanin / Q000378:metabolism / Q000494:pharmacology; D015870:Gene Expression; D006624:Hippocampus / Q000502:physiology; D008024:Ligands; D008297:Male; D018721:Muscarinic Agonists; D010286:Paraventricular Hypothalamic Nucleus / Q000502:physiology; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D010862:Pilocarpine; D011903:Raphe Nuclei / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044091:Receptor, Galanin, Type 1 / Q000235:genetics / Q000378:metabolism; D044092:Receptor, Galanin, Type 2 / Q000235:genetics / Q000378:metabolism; D044093:Receptor, Galanin, Type 3 / Q000235:genetics / Q000378:metabolism; D044088:Receptors, Galanin / Q000235:genetics* / Q000378:metabolism*; D013226:Status Epilepticus / Q000139:chemically induced / Q000503:physiopathology*
D008024:Ligands; D018721:Muscarinic Agonists; D010446:Peptide Fragments; D044091:Receptor, Galanin, Type 1; D044092:Receptor, Galanin, Type 2; D044093:Receptor, Galanin, Type 3; D044088:Receptors, Galanin; D010862:Pilocarpine; D019004:Galanin