Histamine H-1 receptors on peripheral human mononuclear cells were characterized by radioligandbinding of the H-1 receptor antagonist [3H]pyrilamine to lymphocyte-rich preparations. Simultaneous computerized analyses...
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Histamine H-1 receptors on peripheral human mononuclear cells were characterized by radioligandbinding of the H-1 receptor antagonist [3H]pyrilamine to lymphocyte-rich preparations. Simultaneous computerized analyses of 16 separate equilibrium-binding assays indicated the presence of 2 distinct classes of binding sites with dissociation constants (Kds) of 4 .+-. 1 nM and 55 .+-. 9 .mu.M and binding capacities of 21 .+-. 7 fmol and 117 .+-. 15 pmol/million cells, respectively. Competition binding curves for displacement of [3H]pyrilamine binding by histamine receptor agonists and antagonists also indicated the presence of multiple binding sites for the H-1 receptor. Further, the EC50 values determined for histamine receptor agonists and antagonists were entirely consistent with the expected rank order of potency for interactions with H-1 receptors. Thus, human mononuclear cells have a large number of H-1 receptors that exhibit 2 distinct binding sites, and the Kds for these sites are within the range of histamine concentrations achieved either in physiologic states or after mast cell (or basophil) degranulation.
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 c...
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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 .mu.M, and 320 .+-. 167 .mu.M 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 angonist 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-1 antagonist pyrilamine. Thus, human lung possesses a large number of H-2 receptors which exhibit three binding states and produce cyclic GMP, but not cyclic adenosine monophosphate (AMP), when stimulated.
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