In [3H]inositol-labeled membranes prepared from Swiss mouse 3T3 and human small cell lung carcinoma cells, [Tyr4]-bombesin stimulated production of water-soluble inositol phosphates. The reaction was stimulated by guanosine 5′-O-[3-thiotriphosphate] and was specifically inhibited by both [Leu13-ψ-CH2NHLeu14]-bombesin and the antibombesin antibody 2A11. [Tyr4]-bombesin-induced activation of phospholipase C is most apparent in Ca2+-depleted conditions (<1 μm [Ca2+]free). The kinetics of activation by ligand also demonstrate that [Tyr4]-bombesin-dependentphospholipase C activation is most apparent at [Mg2+]free of ~0.2 μ millimolar concentrations of [Mg2+]free, derably less dependence on [Tyr4]-bombesin for activation of phospholipase C. ATP is not necessary for initial activation of phospholipase C, and θ,γ sine-5′phate does not inhibit the reaction. These results demonstrate that in these cell types [Tyr4]-bombesin activates phospholipase C in conjunction with guanine nucleotides. Phospholipase C-coupled guanine nucleotide regulatory proteins would be appropriately considered as novel targets for the development of therapeutic strategies in small cell lung carcinoma.
|Number of pages||6|
|State||Published - 1 Sep 1990|