[125I]Iodobolpyramine, a highly sensitive probe for histamine H1-receptors in guinea-pig brain.
[125I]Iodobolpyramine is a novel 125I-ligand for histamine H1-receptors, synthesised using the 125I-Bolton Hunter reagent (2000 Ci/mmol) for acylation of an aminopentyl analogue of mepyramine. Its specific binding varied linearly with the concentration of guinea-pig cerebellar membranes and represented about 80% of the total. Selective interaction with H1-receptors was demonstrated by estimation of Ki values of known agonists and antagonists and confirmed by the low affinity of histamine H2- and H3-receptor antagonists and of non-histaminergic agents. At 25 degrees C, [125I]iodobolpyramine exhibited a slow association rate (180-240 min to reach equilibrium) and a slow dissociation rate (t1/2 = 201 min). Kinetic and saturation data yielded KD values of 0.05 and 0.15 nM, respectively, indicating that it is among the most potent H1-receptor antagonists known. The sensitivity for detecting H1-receptors in guinea-pig cerebellum using [125I]iodobolpyramine was increased 50-fold relative to use of [3H]mepyramine. Well-contrasted autoradiograms of guinea-pig brain, obtained after a short exposure time, confirmed previous H1-receptor localisation established with [3H]mepyramine and revealed new localisations, e.g. in cerebral cortex and nucleus accumbens.
D000631:Aminopyridines; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007457:Iodine Radioisotopes; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000378:metabolism; D011738:Pyrilamine / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011968:Receptors, Histamine / Q000378:metabolism*; D011969:Receptors, Histamine H1 / Q000378:metabolism*; D013388:Succinimides
D000631:Aminopyridines; D007202:Indicators and Reagents; D007457:Iodine Radioisotopes; D011968:Receptors, Histamine; D011969:Receptors, Histamine H1; D013388:Succinimides; C048171:iodobolpyramine; D011738:Pyrilamine