Carbon-11-forskolin: a ligand for visualization of the adenylate cyclase-related second messenger system.
To visualize the adenylate cyclase (AC)-related second messenger system, [11C]forskolin, [11C]1-acetyl-7-deacetylforskolin, [11C]1,9-dideoxyforskolin and [11C]1-deoxyforskolin were synthesized by acetylation of the respective deacetyl-precursors using [11C]acetylchloride and dimethylaminopyridine. The radiochemical yield of [11C]forskolin, [11C]1-acetyl-7-deacetylforskolin, [11C]1,9-dideoxyforskolin and [11C]1-deoxyforskolin calculated from trapped [11C]CO2 were 5%, 10%, 15% and 18%, respectively. Since the 1- and 9-OH groups on the forskolin structure are critical for specific binding to AC (active type), we considered [11C]1-acetyl-7-deacetylforskolin, [11C]1,9-dideoxyforskolin and [11C]1-deoxyforskolin to be nonspecific forskolin analogs. A comparative study of [11C]forskolin and its analogs on the n-octanol/phosphate buffer (pH 7.4) partition ratio showed that [11C]1-acetyl-7-deacetylforskolin has similar physical properties to [11C]forskolin. In the mouse heart, kidneys, liver and lungs, more [11C]forskolin accumulated than [11C]1-acetyl-7-deacetylforskolin. Moreover, simultaneous [11C]forskolin with forskolin (10 micrograms) administration reduced the accumulation of [11C]forskolin particularly in the heart to the level of [11C]1-acetyl-7-deacetylforskolin. These results indicate that [11C]forskolin would be a useful imaging agent for the AC-related second messenger system.
Sasaki
T
T
Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Japan.
Enta
A
A
Nozaki
T
T
Ishii
S
S
Senda
M
M
D000262:Adenylyl Cyclases / Q000502:physiology*; D000818:Animals; D002250:Carbon Radioisotopes; D005576:Colforsin / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D051379:Mice; D015290:Second Messenger Systems; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D005576:Colforsin; D000262:Adenylyl Cyclases