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Shenzhen Key Laboratory of Metabolic Health, Center for Energy Metabolism and Reproduction, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
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State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen, UK
Institute of Health Sciences, China Medical University, Shenyang, Liaoning, China
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addition to methylxanthines, coffee also contains significant amounts of diterpenoid alcohols or diterpenes, the best known of which are cafestol and kahweol (C&K) ( Fig. 1 ). These are partly degraded during the roasting process into a host of similar
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‘isoprene rule’. In this scenario, C 10 monoterpenes contain two head-to-tail linked hemiterpene isoprene units, C 15 sesquiterpenes contain three C 5 isoprenes, etc. (Box 1). The isoprene rule was extended to accommodate C 20 diterpenes (4 × C 5 = C 20
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ABSTRACT
The effect of diterpene forskolin, a potent stimulator of cyclic AMP (cAMP) in the rat thyroid cell strain FRTL-5, was compared with that of TSH. Forskolin stimulated both the release of cAMP into the culture medium and the accumulation of cAMP in the cytoplasm in a dose-dependent manner, within the range of 0·1–1000 μmol/l. Maximum cAMP concentrations were reached within 15 min of stimulation with forskolin. This is comparable with the effects of TSH. Forskolin also induced morphological changes in cultures of FRTL-5 cells, producing conspicuous cell retraction with arborization and numerous microvilli on the cell surface, specific reorganization of the microfilaments and modulation of the distribution of tubulin and fibronectin. Morphological changes induced by forskolin were always observed 20 to 30 min earlier, and in a higher percentage of cells, than the changes induced by TSH. Cell proliferation, however, was stimulated more effectively by TSH than by forskolin. These observations suggest that TSH might exert its effect on the morphology and growth of FRTL-5 cells, at least in part, through cAMP. The control of morphology and growth might not, however, be regulated solely by the adenylate cyclase and cAMP system.
J. Endocr. (1986) 111, 397–405
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ABSTRACT
A clonal strain of rat thyroid cells (FRTL-5) has been used to investigate the biological activity of a Research Standard preparation of long-acting thyroid stimulator (LATS-B). Using the accumulation of intracellular cyclic AMP as a response parameter, significant stimulation was attained at a LATS-B dose of 0·75 mu./ml. The inter-bioassay coefficient of variation in response to a fixed dose of LATS-B (1·25 mu./ml) was 20·5%, as determined using eight sequential subcultures. Cells cultured directly from frozen stocks responded to both bovine TSH and LATS-B in a manner indistinguishable from cells subjected to regular subculturing. Cyclic AMP responses to incremental doses of LATS-B were potentiated after the inclusion of a low dose of forskolin (0·1 μmol/l). However, forskolin addition had no effect on the time-course of LATS-B-stimulated cyclic AMP accumulation, half-maximal responses being attained after 60 min in either the presence or absence of the diterpene. In the presence of 0·1 μmol forskolin/l, intracellular cyclic AMP responses to LATS-B were demonstrably parallel with those to human TSH (Second International Reference Preparation, 80/558), whilst parallel incremental cyclic AMP responses were also observed in respect of TSH and serial dilutions of a potent thyroid-stimulating immunoglobulin (TSIg) preparation, indicating that for this particular Graves' disease patient, TSIg bioactivity may be expressed in terms of a convenient and reproducible standard, as TSH microunit equivalents.
J. Endocr. (1985) 105, 7–15
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the PLC/PKC and the PKA/cAMP second messenger system serve to amplify nutrient-induced secretion ( Henquin et al. 1987 , Zawalich et al. 1990 ), we probed the effect of elevating cAMP levels using the diterpene forskolin. This pharmacological tool
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. ( https://doi.org/10.1046/j.1471-4159.2003.01894.x ) Laurenza A Sutkowski EM Seamon KB 1989 Forskolin: a specific stimulator of adenylyl cyclase or a diterpene with multiple sites of action? Trends in Pharmacological Sciences 10 442 – 447 . ( https
Academy of Scientific and Innovative Research, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India
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Academy of Scientific and Innovative Research, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India
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Academy of Scientific and Innovative Research, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India
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Academy of Scientific and Innovative Research, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India
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. Histology and Histopathology 28 1411 – 1425 . ( doi:10.14670/HH-28.1411 ) Beg M Shankar K Varshney S Rajan S Singh SP Jagdale P Puri A Chaudhari BP Sashidhara KV Gaikwad AN 2015 A clerodane diterpene inhibit
