Characterisation of the specific binding of the histamine H-3 receptor antagonist radioligand [H-3]GR168320

We have examined the specific binding of the tritiated derivative of the potent histamine H(3) receptor antagonist, [3,4-(3)H(2)]-cyclohexyl-{[4-(3H-imidazol-4-yl)-piperidin-1-yl]iminomethyl}-amine ([(3)H]GR168320), to homogenates of rat cerebral cortex. Specific binding of [(3)H]GR168320 at 37 degrees C associated and dissociated rapidly. Binding was saturable( B(max) 412 +/- 89 fmol/mg protein) and of high affinity (K(d) 0.12 +/- 0.11 nM). Saturation studies suggested the involvement of a single site. Histamine H(3) receptor agonists and antagonists inhibited [(3)H]GR168320 binding with high affinity. Agonist and antagonist affinities correlated when compared with affinities obtained using the tritiated histamine H(3) agonist radioligand N(alpha)-methylhistamine.