Document Detail


Stimulatory and inhibitory effects of forskolin on adenylate cyclase in rat normal hepatocytes and hepatoma cells.
MedLine Citation:
PMID:  2545854     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Forskolin synergistically potentiated adenosine 3',5'-cyclic monophosphate formation by prostaglandin E1 (PGE1) in rat normal hepatocytes freshly prepared by collagenase digestion and rat ascites hepatoma AH66 cells, but dose-dependently inhibited the accumulation by PGE1 in AH66F cells. Forskolin activated adenylate cyclase in a dose-dependent manner in homogenates of all cell lines. In normal hepatocytes and AH66 cells, simultaneous addition of forskolin and other adenylate cyclase activators [isoproterenol (IPN), PGE1, guanosine 5'-triphosphate sodium salt (GTP), 5'-guanylylimidodiphosphate sodium salt (Gpp (NH)p), NaF, cholera toxin, islet activating protein and MnCl2] gave greater than additive responses. On the other hand, in AH66F cells, the effect of forskolin on adenylate cyclase was hardly influenced by GTP, but forskolin diminished the activities induced by high concentrations of GTP to that by the diterpene alone. Forskolin also significantly inhibited the PGE1-stimulated and the guanine nucleotide binding regulatory protein-stimulated activities. Because AH66F cells were insensitive to IPN, the combination with forskolin and IPN gave similar activity to that obtained with the diterpene alone. The effect of forskolin on the activation by manganese ion was neither synergistic nor inhibitory but was additive in AH66F cells. These results suggest that forskolin promotes the interaction between the stimulatory guanine nucleotide binding regulatory protein and the catalytic unit in normal hepatocytes and AH66 cells, but in AH66F cells forskolin interferes with the coupling of the two components of adenylate cyclase.
Authors:
K Miyamoto; F Sanae; R Koshiura; T Matsunaga; K Takagi; T Satake; T Hasegawa
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of pharmacobio-dynamics     Volume:  12     ISSN:  0386-846X     ISO Abbreviation:  J. Pharmacobio-dyn.     Publication Date:  1989 Feb 
Date Detail:
Created Date:  1989-08-22     Completed Date:  1989-08-22     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7901854     Medline TA:  J Pharmacobiodyn     Country:  JAPAN    
Other Details:
Languages:  eng     Pagination:  87-93     Citation Subset:  IM    
Affiliation:
Third Division of the Research Laboratory for Development of Medicine, School of Pharmacy, Hokuriku University, Kanazawa, Japan.
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MeSH Terms
Descriptor/Qualifier:
Adenylate Cyclase / antagonists & inhibitors,  metabolism*
Adenylate Cyclase Toxin
Animals
Cells, Cultured
Cholera Toxin / pharmacology
Cyclic AMP / metabolism
Female
Forskolin / pharmacology*
Guanosine Triphosphate / pharmacology
Liver / cytology,  enzymology*
Liver Neoplasms, Experimental / metabolism*
Manganese / pharmacology
Pertussis Toxin
Proteins / metabolism
Rats
Virulence Factors, Bordetella / pharmacology
Chemical
Reg. No./Substance:
0/Adenylate Cyclase Toxin; 0/Proteins; 0/Virulence Factors, Bordetella; 60-92-4/Cyclic AMP; 66428-89-5/Forskolin; 7439-96-5/Manganese; 86-01-1/Guanosine Triphosphate; 9012-63-9/Cholera Toxin; EC 2.4.2.31/Pertussis Toxin; EC 4.6.1.1/Adenylate Cyclase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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