+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Irreversible inhibition of forskolin interactions with type I adenylyl cyclase by a 6-isothiocyanate derivative of forskolin



Irreversible inhibition of forskolin interactions with type I adenylyl cyclase by a 6-isothiocyanate derivative of forskolin



Molecular Pharmacology 50(2): 299-305



Forskolin (Fsk) has been demonstrated to interact directly with the enzyme adenylyl cyclase (EC 4.6.1.1) in diverse tissues. However, the ability of Fsk to bind to and activate adenylyl cyclase varies depending on the tissue being studied. Different adenylyl cyclase subtypes have been cloned and expressed in a recombinant Sf9 expression system. This provides an opportunity to study the effects of chemically reactive derivatives of Fsk on individual adenylyl cyclase subtypes in the absence of Gs alpha. Reaction of type I adenylyl cyclase with an isothiocyanate derivative of Fsk (6-[[N-(2-isothiocyanatoethyl)amino]carbonyl]forskolin) causes irreversible inhibition of Fsk binding with an IC50 of 300 nM and irreversible inhibition of Fsk activation with an IC50 of 10 microM, suggesting that there are two sites of 6-[[N-(2-isothiocyanatoethyl)amino]carbonyl]forskolin interaction. These studies establish the usefulness of the isothiocyanate derivative of Fsk in localizing the site(s) of Fsk interaction with type I adenylyl cyclase.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 008918982

Download citation: RISBibTeXText

PMID: 8700137


Related references

Interaction of aminoalkylcarbamates of forskolin with adenylyl cyclase: synthesis of an iodinated derivative of forskolin with high affinity for adenylyl cyclase. Molecular Pharmacology 41(2): 360-368, 1992

Conversion of Forskolin-Insensitive to Forskolin-Sensitive (Mouse-Type Ix) Adenylyl Cyclase. Molecular Pharmacology 53(2): 182-187, 1998

Conversion of forskolin-insensitive to forskolin-sensitive (mouse-type IX) adenylyl cyclase. Molecular Pharmacology 53(2): 182-187, 1998

NKH477, an adenylyl cyclase type 5 selective forskolin derivative, inhibits pulmonary artery smooth muscle cell proliferation. Thorax 55(Suppl. 3): A34, 2000

(Aminoalkyl)carbamates of forskolin: intermediates for the synthesis of functionalized derivatives of forskolin with different specificities for adenylyl cyclase and the glucose transporter. Journal of Medicinal Chemistry 34(11): 3204-3212, 1991

Alpha-trinositol blocks the inhibitory effects of NPY on dilatation to forskolin but not the adenylyl cyclase activity induced by NPY or forskolin in guinea-pig cerebral vessels. Neuropeptides 27(5): 259-268, 1994

Inhibition of forskolin-stimulated adenylyl cyclase activity by PD 81,723. Clinical Pharmacology & Therapeutics 59(2): 175, 1996

Interactions of forskolin and ATP with the cytosolic domains of mammalian adenylyl cyclase. Journal of Biological Chemistry 272(35): 22272-7, 1997

Activation and inhibition of adenylyl cyclase isoforms by forskolin analogs. Journal of Pharmacology and Experimental Therapeutics 325(1): 27-36, 2008

Inhibition of forskolin binding by Gpp p may reflect adenylyl cyclase coupling to Gi. Neuroreport 9(14): 3329-3333, 1998

Inhibition of [3H]forskolin binding by Gpp[NH]p may reflect adenylyl cyclase coupling to Gi. Neuroreport 9(14): 3329-3333, 1998

Differential interactions of the catalytic subunits of adenylyl cyclase with forskolin analogs. Biochemical Pharmacology 78(1): 62-69, 2009

Purification of bovine brain adenylyl cyclase with a novel derivative of forskolin: evidence for a high specific activity form of the enzyme. Preparative Biochemistry & Biotechnology 26(2): 155-167, 1996

An adenylyl cyclase stimulating reagent, forskolin, significantly enhanced the CRF-activated adenylyl cyclase activity in hippocampus. FASEB Journal 12(4): A155, 1998

Adenylyl cyclase 3/adenylyl cyclase-associated protein 1 (CAP1) complex mediates the anti-migratory effect of forskolin in pancreatic cancer cells. Molecular Carcinogenesis 56(4): 1344-1360, 2016