Document Detail

Regulation of platelet-activating factor receptor and platelet-activating factor receptor-mediated biological responses by cAMP in rat Kupffer cells.
MedLine Citation:
PMID:  2170386     Owner:  NLM     Status:  MEDLINE    
Treatment of cultured Kupffer cells with the beta-adrenergic agonist isoproterenol (10 microM) for a short period of time (30 min) attenuated the subsequent platelet-activating factor (PAF)-induced arachidonic acid release and cyclooxygenase-derived eicosanoid (e.g. thromboxane B2 and prostaglandin E2) production. This effect of isoproterenol was highly specific since the alpha-adrenergic agonist phenylephrine and the beta-adrenergic antagonist propranolol had no effect on the stimulatory effect of 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (AGEPC). The inhibitory effect of isoproterenol on the AGEPC-induced arachidonic acid release was demonstrated through the use of a specific beta-adrenergic subtype agonist and antagonist to be mediated by beta 2-adrenergic receptors on Kupffer cells. These inhibitory effects of isoproterenol can be mimicked by dibutyryl cAMP but not by dibutyryl cGMP, suggesting that a cAMP-dependent mechanism is likely involved in the regulatory action of isoproterenol. Ligand binding studies indicated that short term (i.e. 30 min) treatment of the cultured Kupffer cells with either isoproterenol or dibutyryl cAMP had no effect on the specific [3H]PAF binding. However, long term incubation (9-24 h) with dibutyryl cAMP caused down-regulation of the PAF receptors in rat Kupffer cells. Forskolin (0.1 mM), an adenylyl cyclase activator, down-regulated the surface expression of the AGEPC receptors more rapidly, decreasing the specific [3H]AGEPC binding by approximately 40% within 2 h. The receptor regulatory effect of dibutyryl cAMP and forskolin was time- and concentration-dependent. These observations suggest that a cAMP-dependent mechanism coupled with beta 2-adrenergic receptors may have important regulatory effects on the PAF receptor and post-receptor signal transducing mechanisms for PAF in hepatic Kupffer cells.
W Chao; H L Liu; W G Zhou; D J Hanahan; M S Olson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  265     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1990 Oct 
Date Detail:
Created Date:  1990-11-21     Completed Date:  1990-11-21     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  17576-83     Citation Subset:  IM    
Department of Biochemistry, University of Texas Health Science Center, San Antonio 78284-7760.
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MeSH Terms
8-Bromo Cyclic Adenosine Monophosphate / pharmacology
Bucladesine / pharmacology*
Cells, Cultured
Cyclic AMP / metabolism,  physiology*
Dinoprostone / metabolism
Forskolin / pharmacology
Isoproterenol / pharmacology
Kupffer Cells / drug effects,  metabolism*
Phenylephrine / pharmacology
Platelet Activating Factor / metabolism,  pharmacology*
Platelet Membrane Glycoproteins*
Receptors, Cell Surface / drug effects,  metabolism*
Receptors, G-Protein-Coupled*
Thromboxane B2 / metabolism
Grant Support
Reg. No./Substance:
0/Platelet Activating Factor; 0/Platelet Membrane Glycoproteins; 0/Receptors, Cell Surface; 0/Receptors, G-Protein-Coupled; 0/platelet activating factor receptor; 23583-48-4/8-Bromo Cyclic Adenosine Monophosphate; 362-74-3/Bucladesine; 363-24-6/Dinoprostone; 54397-85-2/Thromboxane B2; 59-42-7/Phenylephrine; 60-92-4/Cyclic AMP; 66428-89-5/Forskolin; 7683-59-2/Isoproterenol

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