Linked Life Data

8221657

Source:http://linkedlifedata.com/resource/pubmed/id/8221657

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
21
pubmed:dateCreated
1993-11-29
pubmed:abstractText
Gastrin, cholecystokinin (CCK), and CCK-related peptides comprise a hormonal family characterized by an identical carboxy-terminal amino acid sequence, a domain critical for receptor binding. The addition of gastrin to small cell lung cancer (SCLC) cells causes a rapid and transient increase in the intracellular concentration of calcium ([Ca2+]i). Furthermore, gastrin acts as a direct growth factor through CCKB/gastrin receptors. We report here that the expression of the mRNA coding for CCKB/gastrin receptors correlates with the responsiveness of SCLC cells to gastrin in terms of Ca2+ mobilization and stimulation of clonal growth in semisolid medium. The GLC19 SCLC cell line had no detectable expression of CCKB/gastrin receptor mRNA. Accordingly, gastrin (1-100 nM) did not cause any measurable increase in [Ca2+]i. In contrast, the addition of cholecystokinin residues 26-33 (CCK-8) caused a rapid and transient increase in [Ca2+]i in this cell line. CCK-8 mobilized Ca2+ in a dose-dependent manner in the nanomolar range (half-maximal stimulatory concentration = 12 nM). Furthermore, the selective CCKA antagonist CAM-1481 inhibited the increase in [Ca2+]i induced by CCK-8 (half-maximal inhibitory concentration = 3 nM) in GLC19 but not in H510 cells. The selective CCKB/gastrin antagonist blocked the increase in [Ca2+]i induced by CCK-8 (half-maximal inhibitory concentration = 80 pM) in H510 but not in GLC19 cells. Thus, the effects of CCK-8 are mediated through CCKA receptors in GLC19 cells and via CCKB/gastrin receptors in H510 cells. CCK-8 markedly stimulated colony formation in GLC19 cells in a dose-dependent manner in the nanomolar range, whereas over the same concentration range, gastrin had no effect on clonal growth. CAM-1481 inhibited the CCK-stimulated colony formation in GLC19 but not in H510 cells. Our results show, for the first time, that CCKA receptors can mediate Ca2+ mobilization and growth in SCLC cells and that SCLC cells express two distinct functional CCK receptor subtypes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
53
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5208-13
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:8221657-Amino Acid Sequence, pubmed-meshheading:8221657-Animals, pubmed-meshheading:8221657-Base Sequence, pubmed-meshheading:8221657-Blotting, Northern, pubmed-meshheading:8221657-Bradykinin, pubmed-meshheading:8221657-Calcium, pubmed-meshheading:8221657-Carcinoma, Small Cell, pubmed-meshheading:8221657-Clone Cells, pubmed-meshheading:8221657-DNA Primers, pubmed-meshheading:8221657-Dogs, pubmed-meshheading:8221657-Gastrins, pubmed-meshheading:8221657-Gene Expression, pubmed-meshheading:8221657-Humans, pubmed-meshheading:8221657-Kinetics, pubmed-meshheading:8221657-Lung Neoplasms, pubmed-meshheading:8221657-Molecular Sequence Data, pubmed-meshheading:8221657-Muridae, pubmed-meshheading:8221657-Polymerase Chain Reaction, pubmed-meshheading:8221657-RNA, Messenger, pubmed-meshheading:8221657-RNA, Neoplasm, pubmed-meshheading:8221657-Rats, pubmed-meshheading:8221657-Receptors, Cholecystokinin, pubmed-meshheading:8221657-Sequence Homology, Amino Acid, pubmed-meshheading:8221657-Sincalide, pubmed-meshheading:8221657-Tumor Cells, Cultured
pubmed:year
1993
pubmed:articleTitle
CCKA and CCKB receptors are expressed in small cell lung cancer lines and mediate Ca2+ mobilization and clonal growth.
pubmed:affiliation
Imperial Cancer Research Fund, London, England.
pubmed:publicationType
Journal Article, Comparative Study