H1-histamine receptors regulate phosphoinositide hydrolysis in human astrocytoma cells

Activation of H1-histamine receptors on 1321N1 human astrocytoma cells resulted in a rapid formation of the inositol phosphates (InsP), IP3, IP2, and IP1. Histamine-induced mobilization of Ca++ and stimulated of a Ca++ calmodulin-regulated phosphodiesterase occurred concurrently with histamine-stimulated InsP formation. The K/sub 0.5/ values for histamine for activation of phosphodiesterase, mobilization of Ca++, and stimulation of InsP formation were 3,4, and 10 μM, respectively. The K/sub i/ for histamine determined in competition binding experiments with the H1-receptor antagonist, 3H-mepyramine, was 11 μM. As with muscarinic receptor-mediated effects in these cells, inactivation of G/sub i/ with pertussis toxin had no effect on H1-receptor mediated responses. Both histamine and muscarinic receptor stimulation resulted in the formation of Ins 1,4,5P3 and Ins 1,3,4P3. In contrast to muscarinic receptor stimulation, which results in a linear accumulation of InsP for greater than 30 min, histamine-stimulated formation of InsP rapidly desensitized