Abstract:
:Platelet-activating factor (PAF) receptor-coupled activation of phosphoinositide-specific phospholipase C (PLC) was studied in platelets that were made refractory, by short-term pretreatments, to either PAF or thrombin. Generation of [3H]inositol triphosphate ( [3H]IP3) was monitored specifically for this purpose. [3H]Inositol-labeled rabbit platelets that were incubated (10 min) with increasing concentrations of PAF and subsequently challenged by the same concentration of PAF had greatly diminished PLC activity ( [3H]IP3 production) as compared to controls. Platelets incubated (10 min) with fixed concentrations of PAF and then challenged with increasing concentrations of PAF had log-dose response curves of [3H]IP3 production progressively shifted to the right (i.e., to higher concentrations) and were depressed as the PAF pretreatment with 10 nM PAF became completely refractory to further PAF stimulation of PLC. Washing the pretreated platelets with either buffer or buffer containing 0.5% bovine serum albumin did not restore the PAF for 10 min), platelets remained fully responsive to thrombin (2 units/ml)-stimulated production of [3H]IP3. Platelets pretreated with increasing concentrations of thrombin (0.15-2 units/ml) for different times (5-40 min) became refractory to both thrombin and PAF. It is concluded that PAF receptor-coupled activation of PLC becomes refractory (desensitized) in platelets preexposed to PAF, whereas platelets pretreated with thrombin are desensitized to both thrombin and PAF. It is proposed that thrombin has two transmembrane pathways leading to the activation of PLC, one shared with PAF and another utilizing separate mechanistic inputs.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Morrison WJ,Shukla SDsubject
Has Abstractpub_date
1988-01-01 00:00:00pages
58-63issue
1eissn
0026-895Xissn
1521-0111journal_volume
33pub_type
杂志文章abstract::The Gαi/o-coupled dopamine D2-like receptor family comprises three subtypes: the D2 receptor (D2R), with short and long isoform variants (D2SR and D2LR), D3 receptor (D3R), and D4 receptor (D4R), with several polymorphic variants. The common overlap of norepinephrine innervation and D2-like receptor expression pattern...
journal_title:Molecular pharmacology
pub_type: 杂志文章
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journal_title:Molecular pharmacology
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journal_title:Molecular pharmacology
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journal_title:Molecular pharmacology
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1993-08-01 00:00:00
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journal_title:Molecular pharmacology
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1993-11-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1993-02-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
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更新日期:1995-01-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1991-05-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1984-11-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
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