Bombesin-related peptides induce calcium mobilization in a subset of human small cell lung cancer cell lines.
To examine the biochemical basis for growth factor-induced responses in human lung cancer cells, we used the quin2 technique to study the effect of the amphibian peptide bombesin and its congeners including mammalian gastrin-releasing peptide (GRP) on the intracellular free calcium level [Ca2+]i in small cell lung cancer cell lines. In five of eleven cell lines tested, Tyr4-bombesin or GRP elicited a rapid and transient increase in [Ca2+]i. The response was seen with as little as 1 nM ligand, was not affected by membrane depolarization, and derived in part from internal calcium stores. Desensitization to a second addition of active bombesin congeners occurs subsequent to initial addition of Tyr4-bombesin. Structure-activity analysis showed the carboxyl-terminal octapeptide was the active portion of the peptide. Analogs in which the carboxyl terminus was oxidized or deamidated were inactive. Ranatensin, litorin, alytesin, and GRP, but not physalaemin, were as active as Tyr4-bombesin. A monoclonal antibody to the carboxyl terminus of bombesin selectively blocked the increased [Ca2+]i elicited by Tyr4-bombesin. These studies suggest that bombesin congeners can act on some small cell lung cancer cell lines by a pathway utilizing increased [Ca2+]i.
Heikkila
R
R
Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland 20892.
Trepel
J B
JB
Cuttitta
F
F
Neckers
L M
LM
Sausville
E A
EA
D000595:Amino Acid Sequence; D001839:Bombesin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D018288:Carcinoma, Small Cell / Q000378:metabolism*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D019886:Gastrin-Releasing Peptide; D006801:Humans; D007700:Kinetics; D008175:Lung Neoplasms / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D013329:Structure-Activity Relationship
D009842:Oligopeptides; D010455:Peptides; C003291:ranatensin; C000058:alytesin; C010212:litorin; C035891:bombesin, Tyr(4)-; D019886:Gastrin-Releasing Peptide; D001839:Bombesin; D002118:Calcium; D011761:Pyrrolidonecarboxylic Acid