Herzig M C, Chapman W G, Sheridan A, Rake J B, Woynarowski J M
Cancer Therapy and Research Center, Institute for Drug Development, San Antonio, TX 78245, USA.
Anticancer Res. 1999 Jan-Feb;19(1A):213-9.
Second messenger calcium responses to the neuropeptide neurotensin and its non-peptide antagonist SR 48692 were studied in relation to the proliferation of pancreatic cancer cells. Neurotensin caused a transient increase in intracellular calcium in two pancreatic lines, MIA PaCa-2 and PANC-1, with EC50 values of 4.6 and 11.4 nM and peak calcium concentrations of 190% and 470% of basal levels, respectively. SR 48692 inhibited these calcium changes with an IC50 (at 25 nM neurotensin) of 4.9 and 4.1 nM in MIA PaCa-2 and PANC-1 cells, respectively. In MIA PaCa-2 cells, SR 48692 may act as an inverse agonist as it depressed basal calcium. SR 48692 inhibited growth of both MIA PaCa-2 and PANC-1 cells. Only in MIA PaCa-2 cells did neurotensin overcome this inhibition or stimulate proliferation. The results imply that, in MIA PaCa-2 cells, the neurotensin antagonist SR 48692 inhibits growth in a neurotensin receptor-mediated fashion.
研究了第二信使钙对神经肽神经降压素及其非肽拮抗剂SR 48692的反应与胰腺癌细胞增殖的关系。神经降压素在两种胰腺癌细胞系MIA PaCa-2和PANC-1中引起细胞内钙的短暂增加，其半数有效浓度（EC50）值分别为4.6和11.4 nM，钙峰值浓度分别为基础水平的190%和470%。SR 48692抑制这些钙变化，在MIA PaCa-2和PANC-1细胞中，其半数抑制浓度（IC50，在25 nM神经降压素存在时）分别为4.9和4.1 nM。在MIA PaCa-2细胞中，SR 48692可能作为反向激动剂，因为它降低了基础钙水平。SR 48692抑制了MIA PaCa-2和PANC-1细胞的生长。只有在MIA PaCa-2细胞中，神经降压素才能克服这种抑制或刺激增殖。结果表明，在MIA PaCa-2细胞中，神经降压素拮抗剂SR 48692以神经降压素受体介导的方式抑制生长。
