Forskolin (7beta-acetoxy-1alpha,6beta,9alpha-trihydroxy-8,13-epoxy-labd-14-en-11-one) is the first main
labdane diterpenoid isolated from the roots of the Indian Plectranthus barbatus ANDREWS and one of the most extensively studied constituents of this plant. The unique character of
forskolin as a general direct, rapid and reversible activator of
adenylyl cyclase not only underlies its wide range of pharmacological effects but also renders it as a valuable tool in the study of the role of cAMP. The purpose of this review is to provide data presenting the utility of
forskolin--as a cAMP activator--for studying the function of cAMP from different
biological viewpoints as follows: 1) Investigation on the role of cAMP in various cellular processes in different organs such as gastrointestinal tract, respiratory tract, reproductive organs, endocrine system, urinary system, olfactory system, nervous system, platelet aggregating system, skin, bones, eyes, and smooth muscles. 2) Studies on the role of cAMP activation and inhibition to understand the pathogenesis (e.g. thyroid autoimmune
disorders, leukocyte signal transduction defect in depression,
acute malaria infection, secretory dysfunction in inflammatory diseases) as well as its possibly beneficial role for curing diseases such as the regulation of coronary microvascular NO production after
heart failure, the attenuation of the development or progression of
fibrosis in the heart and lungs, the augmentation of myo-protective effects of ischemic preconditioning especially in the failing hearts after
myocardial infarction, the stimulation of the regeneration of injured retinal ganglion cells, the curing of
glaucoma and inflammatory diseases, the reducing of
cyst formation early in the
polycystic kidney disease, and the management of autoimmune disorders by enhancing Fas-mediated apoptosis. 3) Studies on the role of cAMP in the mechanism of actions of a number of drugs and substances such as the effect of the
protoberberine alkaloid palmatine on the active ion transport across rat colonic epithelium, the inhibitory effect of
retinoic acid on HIV-1-induced podocyte proliferation, the whitening activity of
luteolin, the effect of
cilostazol on
nitric oxide production, an effect that is involved in capillary-like tube formation in human aortic endothelial cells, the apoptotic effect of
bullatacin, the effects of
paraoxon and
chlorpyrifos oxon on nervous system. Moreover, cAMP was found to play a role in acute and chronic exposure to
ethanol, in
morphine dependence and withdrawal and in behavioral sensitization to
cocaine as well as in the protection against
cisplatin-induced oxidative injuries.