Linked Life Data

2164025

Source:http://linkedlifedata.com/resource/pubmed/id/2164025

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
1990-8-14
pubmed:abstractText
Prolonged exposure (40 h) of Swiss 3T3 cells to bombesin induced homologous desensitization to bombesin and structurally related peptides including mammalian gastrin releasing peptide (GRP). The ability of bombesin to mobilize intracellular Ca2+, inhibit epidermal growth factor binding, and stimulate DNA synthesis was profoundly and selectively inhibited. In contrast, Ca2+ mobilization by either vasopressin or bradykinin was unaffected, indicating that chronic desensitization is mechanistically distinct from acute desensitization of Ca2+ mobilization. Prolonged (24 or 40 h) pretreatment with bombesin also induced a 78 +/- 5% loss of bombesin receptor binding sites in both intact and plasma membrane preparations of Swiss 3T3 cells without an apparent change in receptor affinity (Kd = 1.9 +/- 0.1 x 10(-9) M and Kd = 1.8 +/- 0.2 x 10(-9) M for control and pretreated cells, respectively). Loss of 125I-GRP binding was slow and progressive with half-maximal loss of binding occurring after 7 h and maximal after approximately 14 h. Cross-linking of 125I-GRP to intact cultures and membrane preparations revealed an identical time-dependent loss of the Mr = 75,000-85,000 cross-linked band, previously identified as the bombesin receptor. Prolonged exposure of the cells to phorbol 12,13-dibutyrate, epidermal growth factor, cholera toxin, or mitogenic combinations of these agents did not alter 125I-GRP binding. Receptor down-regulation and loss of mitogenic responsiveness to bombesin were: (a) induced in a parallel dose-dependent manner by bombesin (ED50 = 1 nM), GRP (ED50 = 2 nM), and neuromedin B (ED50 = 20 nM), but not by the biologically inactive fragment GRP (1-16); (b) inhibited by the specific bombesin antagonist [Leu13-psi(CH2NH)-Leu14] bombesin, and (c) reversed upon removal of bombesin with a similar time course (full recovery after 15 h). On the basis of these observations, we propose that prolonged pretreatment of Swiss 3T3 cells with bombesin induces homologous desensitization to peptides of the bombesin family by down-regulation of cell surface bombesin receptors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
265
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
12052-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:2164025-Animals, pubmed-meshheading:2164025-Bombesin, pubmed-meshheading:2164025-Calcium, pubmed-meshheading:2164025-Cell Membrane, pubmed-meshheading:2164025-Cells, Cultured, pubmed-meshheading:2164025-Cholera Toxin, pubmed-meshheading:2164025-DNA Replication, pubmed-meshheading:2164025-Down-Regulation, pubmed-meshheading:2164025-Epidermal Growth Factor, pubmed-meshheading:2164025-Gastrin-Releasing Peptide, pubmed-meshheading:2164025-Gastrointestinal Hormones, pubmed-meshheading:2164025-Kinetics, pubmed-meshheading:2164025-Mice, pubmed-meshheading:2164025-Molecular Weight, pubmed-meshheading:2164025-Peptides, pubmed-meshheading:2164025-Phorbol 12,13-Dibutyrate, pubmed-meshheading:2164025-Receptor, Epidermal Growth Factor, pubmed-meshheading:2164025-Receptors, Bombesin, pubmed-meshheading:2164025-Receptors, Neurotransmitter
pubmed:year
1990
pubmed:articleTitle
Chronic desensitization to bombesin by progressive down-regulation of bombesin receptors in Swiss 3T3 cells. Distinction from acute desensitization.
pubmed:affiliation
Imperial Cancer Research Fund, Lincoln's Inn Fields, London, United Kingdom.
pubmed:publicationType
Journal Article