TEMPERATURE-DEPENDENCE OF THE BINDING OF [H-3]-LABELED MEPYRAMINE AND RELATED-COMPOUNDS TO THE HISTAMINE-H1 RECEPTOR

  • 1 January 1983
    • journal article
    • research article
    • Vol. 23  (1) , 60-66
Abstract
The extent of the promethazine-sensitive binding of [3H]mepyramine to a washed fraction from guinea pig cerebellum was little altered between 4.degree. and 30.degree.. The dissociation of [3H]mepyramine from the H1 receptor was markedly temperature-sensitive. An Arrhenius plot of the variation of the dissociation rate constant, k-1, with temperature was linear over the range 37.degree.-15.degree. (Ea [activation energy] = 160 kJ mole-1). The association rate constant, k1, was temperature-dependent, and an Arrhenius plot approximated well to a straight line between 30.degree. and 15.degree. (Ea = 112 kJ mole-1). The linear relationship may hold down to 4.degree.. A consequence of the slow dissociation at 4.degree. is that the IC50 [median inhibitory concentration] for mepyramine inhibition of promethazine-sensitive [3H]mepyramine binding at 4.degree. is independent of the concentration of [3H]mepyramine if the cerebellar homogenate is first incubated with the nonradioactive antagonist before addition of the 3H-ligand. Promethazine binding showed a temperture dependence similar to that of mepyramine, and for both antagonists and for chlorpromazine the affinity constant was not greatly increased (equal to or < a factor of 2) at 4.degree. compared with 30.degree.. Tripelennamine showed a more rapid dissociation at 4.degree. than the other antagonists. Mequitazine dissociated slowly at 4.degree., but the affinity constant was lower at 4.degree. than at 30.degree.