[3H]-SB-269970 radiolabels 5-HT7 receptors in rodent, pig and primate brain tissues.
The selective 5-HT7 receptor antagonist radioligand, [3H]-SB-269970, has been reported to radiolabel the human cloned 5-HT7(a) receptor and 5-HT7 receptors in guinea pig cortex (thomas et al, 2000). Saturation analysis of [3H]-SB-269970 binding to mouse forebrain, rat cortex, pig cortex, marmoset cortex and human thalamus membranes was consistent with labelling a homogenous population of binding sites in each tissue. K(D) values for [3H]-SB-269970 binding in these tissues ranged from 0.9 to 2.3 nM, being similar to those reported for the human cloned and guinea pig cortex 5-HT7 receptors (1.3 and 1.7 nM, respectively). Bmax values for [3H]-SB-269970 binding to the mouse, rat, pig, marmoset and human brain membranes were 20, 30, 31, 14 and 68 fmoles x mg x protein(-1), respectively. For each species the profile of inhibition of [3H]-SB-269970 binding, using a number of 5-HT7 receptor agonists and antagonists, correlated well with that reported for the human cloned 5-HT7(a) receptor (correlation coefficients were 0.95, 0.94, 0.92, 0.95, 0.97 versus the mouse, rat, pig, marmoset and human tissues, respectively). In conclusion, [3H]-SB-269970 has been shown to radiolabel 5-HT7 receptors in rodent, pig and primate brain and represents a valuable tool with which to further characterise the distribution and function of 5-HT7 receptors in native tissues and elucidate their potential role in disease states.
Thomas
D R
DR
GlaxoSmithKline Pharmaceuticals, Psychiatry Centre of Excellence for Drug Discovery, New Frontiers Science Park (North), Third Avenue, CM19 5AW, Harlow, Essex, UK. david_r_thomas@sbphrd.com
Atkinson
P J
PJ
Hastie
P G
PG
Roberts
J C
JC
Middlemiss
D N
DN
Price
G W
GW
D000465:Algorithms; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002144:Callithrix; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D051379:Mice; D010636:Phenols; D011869:Radioligand Assay; D019275:Radiopharmaceuticals; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists; D013045:Species Specificity; D013449:Sulfonamides; D013552:Swine
D010636:Phenols; D019275:Radiopharmaceuticals; D011985:Receptors, Serotonin; C404922:SB 269970; D012702:Serotonin Antagonists; D013449:Sulfonamides; C104425:serotonin 7 receptor