Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
|
| pubmed:dateCreated |
1984-11-28
|
| pubmed:abstractText |
Recent studies have suggested that cyclic AMP (cAMP) may be involved in regulation of cell growth and differentiation of cancer cells. Incubating HL-60 cells in the presence of the specific H2 agonist dimaprit resulted in 30-fold increases in cAMP levels (EC50 = 5.7 X 10(-6) M) and morphological changes suggestive of cell maturation along the granulocyte pathway. However, cells cultured with 10(-5) M dimaprit showed more than an 80% decrease in their cAMP response to subsequent addition of H2 agonists, whereas the cAMP response to prostaglandin E2 was unaltered. Desensitization was time-dependent (halftime approximately 2.5 hr with 10(-5) M dimaprit), dose-dependent (dimaprit EC50 = 1.4 X 10(-6) M) and completely prevented by 10(-3) M cimetidine. Desensitization of HL-60 cells for 4 hr with 10(-5) M dimaprit followed by the addition of 10(-3) M cimetidine resulted in total recovery of the cAMP response in less than 24 hr. The pharmacologically inactive analog N-methyldimaprit (SK&F 92054) did not increase cAMP production or cause desensitization to H2 stimulation. Desensitization was observed in the presence or absence of a phosphodiesterase inhibitor, indicating that induction of cAMP-phosphodiesterase was not involved in this process. No difference in the number of [3H]tiotidine binding sites was observed between control and dimaprit-desensitized HL-60 cells. Based on these results, we suggest that H2 receptor agonists caused an agonist-dependent desensitization, presumably due to an uncoupling of receptors from adenylate cyclase.(ABSTRACT TRUNCATED AT 250 WORDS)
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| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/1-Methyl-3-isobutylxanthine,
http://linkedlifedata.com/resource/pubmed/chemical/Cimetidine,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Dimaprit,
http://linkedlifedata.com/resource/pubmed/chemical/Dinoprostone,
http://linkedlifedata.com/resource/pubmed/chemical/Histamine,
http://linkedlifedata.com/resource/pubmed/chemical/Prostaglandins E,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Histamine,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Histamine H2,
http://linkedlifedata.com/resource/pubmed/chemical/Thiocarbamates,
http://linkedlifedata.com/resource/pubmed/chemical/Thiourea,
http://linkedlifedata.com/resource/pubmed/chemical/tiotidine
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Oct
|
| pubmed:issn |
0022-3565
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
231
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1-7
|
| pubmed:dateRevised |
2007-11-15
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| pubmed:meshHeading |
pubmed-meshheading:6208354-1-Methyl-3-isobutylxanthine,
pubmed-meshheading:6208354-Cell Differentiation,
pubmed-meshheading:6208354-Cell Line,
pubmed-meshheading:6208354-Cimetidine,
pubmed-meshheading:6208354-Cyclic AMP,
pubmed-meshheading:6208354-Dimaprit,
pubmed-meshheading:6208354-Dinoprostone,
pubmed-meshheading:6208354-Dose-Response Relationship, Drug,
pubmed-meshheading:6208354-Histamine,
pubmed-meshheading:6208354-Humans,
pubmed-meshheading:6208354-Leukemia, Myeloid, Acute,
pubmed-meshheading:6208354-Prostaglandins E,
pubmed-meshheading:6208354-Receptors, Histamine,
pubmed-meshheading:6208354-Receptors, Histamine H2,
pubmed-meshheading:6208354-Thiocarbamates,
pubmed-meshheading:6208354-Thiourea
|
| pubmed:year |
1984
|
| pubmed:articleTitle |
Histamine H2 receptor desensitization in HL-60 human promyelocytic leukemia cells.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|