The initial inositol 1,4,5-trisphosphate response induced by histamine is strongly amplified by Ca2+ release from internal stores in smooth muscle

We have studied the Ca2+-dependence and wortmannin-sensitivity of the initial inositol 1, 4,5-trisphosphate (Ins(1,4,5)P-3) response induced by activation of either histamine or muscarinic receptors in smooth muscle from guinea pig urinary bladder. Activation of H-1 receptors with histamine (100 muM) produced a significant elevation in Ins(1,4,5)P-3 levels with only 5s stimulation and in the presence of external Ca2+. However, this response was abolished fully by either the prolonged absence of external Ca2+ or the depletion of internal Ca2+ stores with thapsigargin (100 nM) or ryanodine (10 muM). In contrast, the same conditions only slightly reduced the initial Ins(1,4,5)P-3 response induced by carbachol. The prolonged incubation of smooth muscle in 10 muM wortmannin to inhibit type III PI 4-kinase abolished both the early histamine-evoked Ins(1,4,5)P-3 and Ca2+ responses. Conversely, wortmannin did not alter Ca2+ release induced by carbachol, despite a partial reduction of its Ins(1,4,5)P-3 response. Collectively, these data indicate that the detectable histamine-induced increase in Ins(1,4,5)P-3 is more the consequence of Ca2+ release from internal stores than a direct activation of phospholipase C by H-1 receptors. In addition, the effect of wortmannin implies the existence of a Ca2+-dependent amplification loop for the histamine-induced Ins(1,4,5)P-3 response in smooth muscle. (C) 2002, Elsevier Science Ltd. All rights reserved.