Characterisation of the specific binding of the histamine H3 receptor antagonist radioligand [3H]GR168320.
We have examined the specific binding of the tritiated derivative of the potent histamine H3 receptor antagonist, [3,4-3H2]-cyclohex-yl-¿[4-(3H-imidazol-4-yl)-piperidin-l-yl] iminomethyl¿- amine ([3H]GR168320), to homogenates of rat cerebral cortex. Specific binding of [3H]GR168320 at 37 degrees C associated and dissociated rapidly. Binding was saturable (Bmax 412 +/- 89 fmol/mg protein) and of high affinity (Kd 0.12 +/- 0.11 nM). Saturation studies suggested the involvement of a single site. Histamine H3 receptor agonists and antagonists inhibited [3H]GR168320 binding with high affinity. Agonist and antagonist affinities correlated when compared with affinities obtained using the tritiated histamine H3 agonist radioligand N alpha-methylhistamine.
Brown
J D
JD
Department of Pharmacology, Glaxo Research & Development Ltd., Stevenage, Hertfordshire, UK.
O'Shaughnessy
C T
CT
Kilpatrick
G J
GJ
Scopes
D I
DI
Beswick
P
P
Clitherow
J W
JW
Barnes
J C
JC
D000818:Animals; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000378:metabolism*; D007093:Imidazoles / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008761:Methylhistamines / Q000378:metabolism*; D011869:Radioligand Assay; D051381:Rats; D018100:Receptors, Histamine H3 / Q000378:metabolism*
C103528:GR 168320; D007093:Imidazoles; D008761:Methylhistamines; D018100:Receptors, Histamine H3