Pituitary adenylate cyclase activating polypeptide receptors are present on small cell lung cancer cells.
The effect of pituitary adenylate cyclase activating polypeptide (PACAP) on small cell lung cancer (SCLC) cells was investigated. In Fura 2-AM loaded NCI-N417 cells, PACAP-27 or PACAP-38 elevated cytosolic calcium in a dose-dependent manner. The cytosolic calcium was elevated from 133 to 185 nM with PACAP-27 (100 nM). Because PACAP-27 strongly elevated cytosolic calcium after the addition of 1 mM EGTA, PACAP released calcium from intracellular pools using NCI-N417 cells; similar results were obtained for SCLC cell line NCI-H345. Pituitary adenylate cyclase activating polypeptide-27 inhibited 125I-VIP and 125I-PACAP binding to NCI-N417 cells with high affinity (IC50 = 30 and 5 nM), whereas VIP inhibited 125I-VIP and 125I-PACAP-27 binding with IC50 values of 5 and 200 nM. Both 100 nM VIP and PACAP-27 elevated cAMP levels in NCI-H345 cells. In contrast, 1 microM VIP had no effect on cytosolic calcium, whereas 100 nM PACAP-27 caused a strong calcium response. Both 100 nM VIP and 10 nM PACAP-27 significantly stimulated the clonal growth of NCI-H345 cells. These data suggest that biologically active VIP and PACAP receptors are present on SCLC cells.
Department of Biochemistry and Molecular Biology, George Washington University School of Medicine and Health Sciences, Washington, DC 20037.
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Moody
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Makheja
D000595:Amino Acid Sequence; D002118:Calcium / Q000378:metabolism; D018288:Carcinoma, Small Cell / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D011964:Receptors, Gastrointestinal Hormone / Q000378:metabolism; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D011979:Receptors, Pituitary Hormone; D018005:Receptors, Vasoactive Intestinal Peptide; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000737:chemistry / Q000378:metabolism
C495401:ADCYAP1 protein, human; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011956:Receptors, Cell Surface; D011964:Receptors, Gastrointestinal Hormone; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D011979:Receptors, Pituitary Hormone; D018005:Receptors, Vasoactive Intestinal Peptide; D014660:Vasoactive Intestinal Peptide; D000242:Cyclic AMP; D002118:Calcium