neurokinin-a and Neuroblastoma

We found that neurokinin A (NKA) and neurokinin B (NKB) induce an increase in the concentration of intracellular free Ca2+ ([Ca2+]i) in murine neuroblastoma C1300 cells (EC50: NKA 87 +/- 13 nM, NKB 97 +/- 15 nM). Substance P (SP) also caused a transient Ca2+ increase, although the potency of SP was much less than that of NKA and NKB. The increase in [Ca2+]i induced by NKA and NKB was inhibited by SR 48,968, a selective antagonist for NK2, and [beta Ala8]NKA(4-10), a selective agonist for NK2, did not stimulate the increase in [Ca2+]i. NKA- and NKB-induced Ca2+ mobilization was not inhibited by CP-96,345 and [Trp7, beta Ala8]NKA(4-10), selective antagonists for NK1 and NK3, respectively. These results suggested that C1300 cells express endogenous NK2 neurokinin receptors that have different features from known NK2 receptors.

Topics: Animals; Benzamides; Calcium; Cell Line; Kinetics; Mice; Neuroblastoma; Neurokinin A; Neurokinin B; Piperidines; Receptors, Tachykinin; Substance P; Tumor Cells, Cultured

Factors regulating differentiation of the peripheral nervous system (PNS) have been widely studied in neuroblastomas which are tumors of the PNS. Five neuroblastomas were investigated for their content of tachykinin neuropeptides, which arise from two distinct genes which appear differentially expressed in the PNS. Radioimmunoassay and column chromatography revealed large amounts of neurokinin B in three of these tumors and the absence of substance P, neurokinin A, neuropeptide K and neuropeptide gamma from all five tumors. This suggests that neuroblastomas can selectively express the preprotachykinin (PPT) II gene and that they may be valuable for investigating the factors involved in the regulation of these two structurally-related neuropeptide genes.

Topics: Chromatography, High Pressure Liquid; Gene Expression; Humans; Neuroblastoma; Neurokinin A; Neurokinin B; Protein Precursors; Radioimmunoassay; Substance P; Tachykinins