Quantitative autoradiography of 5-HT4 receptors in brains of three species using two structurally distinct radioligands, [3H]GR113808 and [3H]BIMU-1.
Recent radioligand binding studies have demonstrated the presence of 5-HT4 receptors throughout the nigrostriatal and mesolimbic systems of mammalian brain. In many regions, the binding has not yet been correlated with functional responses. The present study was carried out to fully characterize the regional distribution of 5-HT4 receptors in brain sections from three species using two structurally distinct radioligands, [3H]GR113808, and [3H]BIMU-1. The highest density of 5-HT4 receptors labeled with [3H]GR113808 was found in the olfactory tubercle, substantia nigra, ventral pallium and striatum of rat and guinea pig, and similar regions of pig-tail macaque monkey. A similar distribution of 5-HT4 receptors was observed in guinea pig brain using [3H]BIMU-1. With either ligand, the binding was saturable and of high affinity (Kd = 0.08-0.53 nM for [3H]GR113808; 1.4-3.0 nM for [3H]BIMU-1). These results extend previous distribution studies, confirm the heterogenous distribution of 5-HT4 receptors throughout the nigrostriatal and mesolimbic systems of three species, and demonstrate a similar distribution using two structurally distinct 5-HT4 radioligands.
Department of Neurosciences, Institute of Pharmacology, Palo Alto, CA 94303.
L B
LB
Jakeman
Z P
ZP
To
R M
RM
Eglen
E H
EH
Wong
D W
DW
Bonhaus
D000818:Animals; D001345:Autoradiography; D001562:Benzimidazoles / Q000493:pharmacokinetics; D001921:Brain / Q000033:anatomy & histology*; D001923:Brain Chemistry / Q000187:drug effects*; D001643:Bridged Bicyclo Compounds / Q000493:pharmacokinetics; D019086:Bridged Bicyclo Compounds, Heterocyclic; D006168:Guinea Pigs; D006220:Haloperidol / Q000494:pharmacology; D007211:Indoles / Q000493:pharmacokinetics; D008024:Ligands; D008251:Macaca; D008254:Macaca nemestrina; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000493:pharmacokinetics; D013045:Species Specificity; D013449:Sulfonamides / Q000493:pharmacokinetics
D001562:Benzimidazoles; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007211:Indoles; D008024:Ligands; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013449:Sulfonamides; C070187:(endo-N-8-methyl-8-azabicyclo(3.2.1)oct-3-yl)-2,3-dihydro-3-ethyl-2-oxo-1H-benzimidazol-1-carboxamide; D006220:Haloperidol; C082871:GR 113808