Characterization of histamine H-1 receptors on human peripheral lung

Biochemical Pharmacology
T B CasaleM Kaliner


Histamine H-1 receptors in human peripheral lung were characterized by radioligand and biochemical assays employing binding of the H-1 receptor antagonist [3H]pyrilamine to plasma membrane preparations. Simultaneous computerized analyses of the data from fourteen separate equilibrium-binding assays indicated the presence of three distinct classes of binding sites with Kd values of 81 +/- 35 pM, 7 +/- 3 microM, and 320 +/- 167 microM and binding capacities of 23 +/- 3 pmoles, 10 +/- 5 nmoles, and 297 +/- 119 nmoles/mg protein respectively. Dissociation kinetics of [3H]pyrilamine binding also supported the presence of three binding sites or states. Further, competition binding curves for histamine receptor agonists and antagonists also indicated the presence of multiple binding sites for the H-1 receptor. The effect of exogenous stimulation of histamine H-1 receptors on human cyclic nucleotides was also examined. Both histamine and the H-1 agonist 2-methyl histamine caused dose-related increases in the cyclic guanosine monophosphate (GMP) content of human lung. The effects of 2-methyl histamine were selective for cyclic GMP. The histamine-induced increase in cyclic GMP peaked within 1.0 min and was effectively prevented by the H-...Continue Reading


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