The release of bombesin-like peptides from small cell lung cancer cells. 1988

T W Moody, and L Y Korman
Department of Biochemistry, George Washington University School of Medicine and Health Sciences, Washington.

High levels of BN/GRP are present in classic SCLC and lung carcinoids, whereas BN immunoreactivity is absent in variant SCLC, adenocarcinoma, large cell carcinoma, squamous cell carcinoma, and mesothelioma cell lines. BN-like peptides are secreted from classic SCLC into the tissue culture medium. The secretion rate of BN-like peptides from cell line NCI-H345 was increased 3-fold by VIP (1 microM). Also, VIP increased the cAMP levels in cell line NCI-H345 by an order of magnitude. Therefore, SCLC cells have functional VIP receptors which regulate the secretion of BN-like peptides. Also, SRIF (100 nM) inhibits the VIP-stimulated increase in cAMP levels and secretion rate of BN-like peptides from SCLC cells. Because BN stimulates colony formation, VIP and/or SRIF may be able to alter the growth of SCLC cells. BN-like peptides are secreted from SCLC cells into the plasma. The levels of BN immunoreactivity in the plasma of SCLC patients with extensive disease is 2- to 40-fold greater than that of patients with limited disease. Secretin infusion into patients with extensive disease produces a transient increase (7-fold) in the plasma concentration of BN-like peptides. BN-like peptides are also present in the CSF of SCLC patients. When released from SCLC cells, BN-like peptides may interact with cell surface receptors. [Tyr4]BN binds with high affinity (Kd = 0.5 nM) to a single class of sites (1500/cell) on cell line NCI-H345. The carboxyl terminus of BN or GRP is essential for high-affinity binding activity. BN-like peptides elevate cytosolic Ca2+ levels as a result of increased phosphatidylinositol turnover. The putative BN receptor antagonist [D-Arg1, D-Pro2, D-Trp7,9, Leu11]substance P inhibits high-affinity [Tyr4]BN binding, the ability of BN to elevate cytosolic Ca2+ levels, and colony formation of SCLC cells. Therefore, BN receptor antagonists may serve as useful agents to inhibit the growth of SCLC.

UI MeSH Term Description Entries
D008175 Lung Neoplasms Tumors or cancer of the LUNG. Cancer of Lung,Lung Cancer,Pulmonary Cancer,Pulmonary Neoplasms,Cancer of the Lung,Neoplasms, Lung,Neoplasms, Pulmonary,Cancer, Lung,Cancer, Pulmonary,Cancers, Lung,Cancers, Pulmonary,Lung Cancers,Lung Neoplasm,Neoplasm, Lung,Neoplasm, Pulmonary,Pulmonary Cancers,Pulmonary Neoplasm
D010455 Peptides Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS. Peptide,Polypeptide,Polypeptides
D001839 Bombesin A tetradecapeptide originally obtained from the skins of toads Bombina bombina and B. variegata. It is also an endogenous neurotransmitter in many animals including mammals. Bombesin affects vascular and other smooth muscle, gastric secretion, and renal circulation and function. Bombesin 14,Bombesin Dihydrochloride,Dihydrochloride, Bombesin
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012633 Secretin A peptide hormone of about 27 amino acids from the duodenal mucosa that activates pancreatic secretion and lowers the blood sugar level. (USAN and the USP Dictionary of Drug Names, 1994, p597) Secrepan,Secretin Citrate, Pig,Secretin Maleate, Pig,Secretin Pentacetate, Pig,Secretin Sulfate, Pig,Secretin, Pig,Secretin-KABI,Pig Secretin,Pig Secretin Citrate,Pig Secretin Maleate,Pig Secretin Pentacetate,Pig Secretin Sulfate,Secretin KABI,SecretinKABI
D014660 Vasoactive Intestinal Peptide A highly basic, 28 amino acid neuropeptide released from intestinal mucosa. It has a wide range of biological actions affecting the cardiovascular, gastrointestinal, and respiratory systems and is neuroprotective. It binds special receptors (RECEPTORS, VASOACTIVE INTESTINAL PEPTIDE). VIP (Vasoactive Intestinal Peptide),Vasoactive Intestinal Polypeptide,Vasointestinal Peptide,Intestinal Peptide, Vasoactive,Intestinal Polypeptide, Vasoactive,Peptide, Vasoactive Intestinal,Peptide, Vasointestinal,Polypeptide, Vasoactive Intestinal
D017981 Receptors, Neurotransmitter Cell surface receptors that bind signalling molecules released by neurons and convert these signals into intracellular changes influencing the behavior of cells. Neurotransmitter is used here in its most general sense, including not only messengers that act to regulate ion channels, but also those which act on second messenger systems and those which may act at a distance from their release sites. Included are receptors for neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not located at synapses. Neurohumor Receptors,Neuromediator Receptors,Neuromodulator Receptors,Neuroregulator Receptors,Receptors, Neurohumor,Receptors, Synaptic,Synaptic Receptor,Synaptic Receptors,Neuromediator Receptor,Neuromodulator Receptor,Neuroregulator Receptor,Neurotransmitter Receptor,Receptors, Neuromediators,Receptors, Neuromodulators,Receptors, Neuroregulators,Receptors, Neurotransmitters,Neuromediators Receptors,Neuromodulators Receptors,Neuroregulators Receptors,Neurotransmitter Receptors,Neurotransmitters Receptors,Receptor, Neuromediator,Receptor, Neuromodulator,Receptor, Neuroregulator,Receptor, Neurotransmitter,Receptor, Synaptic,Receptors, Neuromediator,Receptors, Neuromodulator,Receptors, Neuroregulator
D018004 Receptors, Bombesin Cell surface proteins that bind bombesin or closely related peptides with high affinity and trigger intracellular changes influencing the behavior of cells. Gastrin- releasing peptide (GRP); GRP 18-27 (neuromedin C), and neuromedin B are endogenous ligands of bombesin receptors in mammals. Bombesin Receptors,Gastrin-Releasing Peptide Receptors,Neuromedin B Receptors,Receptors, Gastrin-Releasing Peptide,Receptors, Neuromedin B,Bombesin Receptor,Gastrin-Releasing Peptide Receptor,Neuromedin B Receptor,B Receptor, Neuromedin,B Receptors, Neuromedin,Gastrin Releasing Peptide Receptor,Gastrin Releasing Peptide Receptors,Peptide Receptor, Gastrin-Releasing,Peptide Receptors, Gastrin-Releasing,Receptor, Bombesin,Receptor, Gastrin-Releasing Peptide,Receptor, Neuromedin B,Receptors, Gastrin Releasing Peptide
D018288 Carcinoma, Small Cell An anaplastic, highly malignant, and usually bronchogenic carcinoma composed of small ovoid cells with scanty neoplasm. It is characterized by a dominant, deeply basophilic nucleus, and absent or indistinct nucleoli. (From Stedman, 25th ed; Holland et al., Cancer Medicine, 3d ed, p1286-7) Carcinoma, Oat Cell,Oat Cell Carcinoma,Small Cell Carcinoma,Carcinomas, Oat Cell,Carcinomas, Small Cell,Oat Cell Carcinomas,Small Cell Carcinomas

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