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Research Articles
Coleus Forskohlii (forskolin)
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Acta Diabetol Lat 1991 Jan-Mar;28(1):71-7 |
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Insulin and glucagon releasing activity of
coleonol (forskolin) and its effect on blood glucose level in normal
and alloxan diabetic rats.
Ahmad F, Khan MM,
Rastogi
AK, Kidwai JR.
Division of Biochemistry, Central Drug Research Institute, Lucknow,
India.
Colenol, a diterpenoid isolated from the roots of Coleus forskohlii
stimulates the release of insulin and glucagon from the islets both
in vitro and in vivo. Colenol-stimulated release of glucagon from
islets in vitro is much more pronounced as compared to that of
insulin. Glucose concentration of 5.6 mM in the medium is required
for the colenol stimulation of insulin release. Feeding of coleonol
to alloxan diabetic rats cause 36.5% increase in blood glucose level
as compared to alloxan diabetic control. Oral feeding of coleonol
for 7 days to normal rats causes increase in blood glucose, serum
insulin, glucagon and free fatty acid levels with corresponding
increase in glucose-6-phosphatase activity and depletion of liver
glycogen. Predominant stimulation of A-cells by coleonol is
suggested for the above effects.
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Arzneimittelforschung 1981;31(8):1248-50 |
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The positive inotropic-acting forskolin, a
potent adenylate cyclase activator.
Metzger H, Lindner E.
Forskolin is a positive inotropic-acting and blood pressure lowering
agent which was isolated from the Indian plant Coleus forskohlii. In
isolated heart tissue, forskolin activates a membrane bound
adenylatecyclase and a cytoplasmic cAMP-dependent protein kinase to
a much higher degree than does isoprenaline. This activation does
not require the hormone receptor. In isolated and electrically
stimulated left guinea pig atria, the adenylate-cyclase activation
by forskolin is the prerequisite for the positive inotropic effect.
We therefore postulate the adenylatecyclase activation to be
correlated with the positive inotropic effect via an enhanced
calcium uptake by the heart muscle cell.
Pharmacological studies on coleonol, a hypotensive diterpene from
Coleus forskohlii.
Dubey MP, Srimal RC, Nityanand S, Dhawan BN.
Coleus spp. have been used in Aurvedic medicine for heart diseases,
spasmodic pain, painful micturition and convulsions. The
pharmacological properties of coleonol, a diterpene, isolated from
Coleus forskohlii were investigated. Its predominant effect is to
lower the blood pressure of anaesthetised cat and rat as well as of
the spontaneously hypertensive rat due to relaxation of the vascular
smooth muscle. In small doses it has a positive inotropic effect on
isolated rabbit heart as well as on cat heart in vivo. Coleonol also
exhibits nonspecific spasmolytic activity on smooth muscle of the
gastrointestinal tract in various species but not on bronchial
musculature of guinea pig. Large doses of coleonol have a depressant
action on the central nervous system. These results provide the
rationale for the use of this plant in Aurvedic medicine.
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Trends Pharmacol Sci 1989 Nov;10(11):442-7 |
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Forskolin: a specific stimulator of adenylyl
cyclase or a diterpene with multiple sites of action?
Laurenza A, Sutkowski EM, Seamon KB.
Forskolin, a naturally occurring diterpene, directly stimulates
adenylyl cyclase and has been used extensively to increase cAMP and
to elicit cAMP-dependent physiological responses. More recently,
forskolin has been shown to inhibit a number of membrane transport
proteins and channel proteins through a mechanism that does not
involve the production of cAMP. Many of these channel proteins are
predicted to have similar topographies in the membrane bilayer and
it is tempting to speculate that forskolin may be binding at
structurally homologous sites. Kenneth Seamon and colleagues discuss
the cAMP-independent effects of forskolin and the structural
similarity between forskolin and other physiologically important
substances such as hexoses and steroids with respect to potential
forskolin binding sites.
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Endocrinology 1982 Sep;111(3):849-56 |
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Forskolin stimulation of thyroid adenylate
cyclase and cyclic 3',5'-adenosine monophosphate accumulation.
Fradkin JE, Cook GH, Kilhoffer MC, Wolff J.
The diterpene forskolin is a potent (100-fold) stimulator of guinea
pig thyroid cAMP accumulation with half-maximal activation occurring
at 40 microM. Forskolin stimulation is more rapid than that of TSH,
attaining a 5-fold increase within 1 min of exposure. The
stimulation is also rapidly reversible. The diterpene does not
sensitize thyroid cAMP accumulation to TSH, and the concentration
yielding half-maximal response is not altered by the presence of low
levels of forskolin. At maximally stimulating concentrations, the
effects of TSH and forskolin on cAMP accumulation are additive.
Forskolin stimulates thyroid adenylate cyclase approximately 10-fold
in membranes from several species with half-maximal effects
occurring at 3--9 microM through an action on the maximum velocity
and not the Km for ATP. The activation of thyroid membranes is
readily reversible. Guanyl nucleotides are not required for
stimulation by forskolin, and they do not sensitize to forskolin.
Moreover, the drug did not sensitize the membrane adenylate cyclase
to guanosine 5'-[beta, gamma-imido]triphosphate or to isoproterenol
and was equally effective with either Mg++ or Mn++ as the divalent
cation. Forskolin stimulation is additive with that of guanyl
nucleotides and F-. The site of action of forskolin in the adenylate
cyclase complex is uncertain. Data from Bordetella pertussis,
testicular, and S-49 lymphoma mutant cyclases suggest that one of
the guanyl nucleotide regulatory proteins may be required to promote
the forskolin effect. We conclude that forskolin is a useful
activator of thyroid adenylate cyclase both in vitro and in intact
tissue, which will be useful in elucidating the coupling process of
the adenylate cyclase system and in differentiating cAMP-mediated
from other forms of activation of the thyroid.
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Acta Endocrinol (Copenh) 1985 Feb;108(2):200-5 |
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Forskolin stimulation of adenylate cyclase in
human thyroid membranes.
Kasai K, Suzuki Y, Hiraiwa M, Kuroda H, Emoto T, Nakamura T,
Shimoda S.
Forskolin stimulates adenylate cyclase in human thyroid membranes
approximately 7-fold with half-maximal stimulation occurring at 5-10
microM. Guanine nucleotides are not required for stimulation of the
enzyme by forskolin. Forskolin-stimulation is additive or greater
than additive with that of TSH or Gpp(NH)p- (above 1 microM).
Different from TSH- or Gpp(NH)p-stimulation of adenylate cyclase,
uncoupling of the guanine nucleotide-binding regulatory component by
increasing concentrations of MnCl2 did not result in uncoupling of
forskolin stimulation. The finding indicates that forskolin may
mainly act on the catalytic component of adenylate cyclase. From the
present study, it is suggested that the diterpene forskolin
stimulates adenylate cyclase in human thyroid membranes by a novel
mechanism that differs from TSH- or Gpp(NH)p-stimulation, and that
the diterpene may be a useful tool to investigate the metabolism of
thyroid and its regulation in normal and pathological situations.
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