THE BINDING OF [³H]MEPYRAMINE TO HISTAMINE H₁ RECEPTORS IN GUINEA‐PIG BRAIN

Abstract

Abstract The promethazine‐sensitive binding of [ 3 H]mepyramine to a membrane fraction from guinea‐pig whole brain is saturable with a dissociation constant of 1.7 × 10 ‐9 M. The maximum amount of [ 3 H]mepyramine binding varied widely between preparations, range 122–365 pmol/g protein, with a mean value of 227 ± 52 pmol/g protein. The inhibition of [ 3 H]mepyramine binding by a number of drugs correlated closely with their potency as histamine H 1 antagonists. (+) Chlorpheniramine was 240‐fold more potent as an inhibitor of [ 3 H]mepyramine binding than (‐)‐chlorpheniramine. All antagonists inhibited the binding of [ 3 H]mepyramine to the same extent, but the Hill coefficients characterising the inhibition curves did not all approximate to unity, the value expected for a simple antagonist‐receptor equilibrium. The distribution of histamine H 1 receptors, defined by the promethazine‐sensitive binding of [ 3 H]mepyramine, in 11 different brain regions was uneven with the largest amounts in cerebellum, superior and inferior colliculus and hypothalamus and the smallest in caudate nucleus, brain stem and spinal cord.