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121.
Leatherland JF Lin L Renaud R 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》2005,140(4):647-656
The effects of glutamate and somatostatin-14 (SRIF) on the in vitro basal and cAMP-stimulated steroid production of mid-vitellogenic rainbow trout (Oncorhynchus mykiss) ovarian follicles were investigated. cAMP-stimulation was achieved by the addition of the adenylyl cyclase activator, forskolin (FS), or a membrane permeate cAMP agonist, 8-bromo-cAMP (BA), to the incubation medium. Testosterone (T) and 17β-estradiol (E2) secretion was measured using radioimmunoassay. Solid phase extraction (SPE) was used to measure the relative formation of unconjugated and conjugated steroids, and high performance liquid chromatography (HPLC) was used to examine the steroid metabolites formed from the metabolism of a tritium labelled precursor, pregnenolone (P5). The accumulations of T and E2 in the medium were suppressed in the presence of the glutamate agonists, N-methyl-d,l-aspartate (NMA) or l-glutamic acid (GA), and by the presence of SRIF. The suppression was evident for both basal and cAMP-stimulated steroidogenesis except for T concentrations of GA treatments following basal steroidogenesis, when there were no treatment effects. No significant effects of treatment on conjugated:unconjugated steroid ratios were found. For all treatments E2 was the major end product steroid synthesized from P5, and the steroid profiles were similar except for trace amounts of radiolabelled androgens in the medium following cAMP-stimulated steroidogenesis that were not present following basal steroidogenesis. The findings suggest that glutamate and SRIF reduce end point steroid production, possibly by reducing P5 production. However, since the inhibitory affect was found for basal and cAMP-stimulated steroidogenesis, the response does not appear to be due to the inhibition of cAMP synthesis. 相似文献
122.
123.
Berk A Fronius M Clauss W Schnizler M 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》2004,174(1):83-89
The apical mucus on pulmonary epithelia is not only critical for physiological functions such as gas exchange or inflammatory processes, but also contains surfactants and multiple molecules that mediate cellular responses. A tight control of transepithelial ion transport maintains viscosity of this layer and, e.g., the amiloride-sensitive sodium channels (ENaCs) in lung epithelia of vertebrates are the most important regulatory sites for transcellular sodium uptake. Dysfunction of this sodium transport results in reduced liquid absorption and causes massive problems with gas exchange. We used dissected lungs of Xenopus laevis in Ussing chambers to investigate the influence of prostaglandin E2 (PGE2) on the regulation of short-circuit current (I
SC) and amiloride-sensitive sodium absorption (I
ami). Apical application of PGE2 (1 M) increased I
SC by 38% and I
ami by approximately 60%. In contrast, a different prostaglandin, PGI2, neither affected I
SC nor I
ami. Forskolin increased current to a similar magnitude and preincubation of the lung with an RP-isomer of cyclic AMP, an inhibitor of proteinkinase A (PKA), abolished the effects of both PGE2 and forskolin. Transepithelial Na+ uptake was also upregulated by the prostaglandin receptor agonists misoprostol and sulprostone . The I
ami in Xenopus oocytes that heterologously expressed ENaCs was not affected by PGE2.Abbreviations ACTH
adrenocorticotropic hormone
-
ENaC
epithelial sodium channel
-
hENaC
epithelial sodium channels from human lung
-
ORI
oocyte Ringers solution
-
PKA
protein kinase A
-
R
T
transepithelial resistance
-
V
T
transepithelial potential
-
xENaC
epithelial sodium channels from Xenopus nephron
-
I
ami
amiloride-sensitive current
-
I
SC
short-circuit current
-
NRS
normal Ringers solution
-
PGE
2
prostaglandin E2
Communicated by G. Heldmaier 相似文献
124.
In cystic fibrosis airway epithelia, mutation of the CFTR protein causes a reduced response of Cl− secretion to secretagogues acting via cAMP. Using a Ca2+ imaging system, the hypothesis that CFTR activation may permit ATP release and regulate [Ca2+]
i
via a receptor-mediated mechanism, is tested in this study. Application of external nucleotides produced a significant increase
in [Ca2+]
i
in normal (16HBE14o− cell line and primary lung culture) and in cystic fibrosis (CFTE29o− cell line) human airway epithelia. The potency order of nucleotides on [Ca2+]
i
variation was UTP ≫ ATP > UDP > ADP > AMP > adenosine in both cell types. The nucleotide [Ca2+]
i
response could be mimicked by activation of CFTR with forskolin (20 μm) in a temperature-dependent manner. In 16HBE14o− cells, the forskolin-induced [Ca2+]
i
response increased with increasing temperature. In CFTE29o− cells, forskolin had no effect on [Ca2+]
i
at body temperature-forskolin-induced [Ca2+]
i
response in CF cells could only be observed at low experimental temperature (14°C) or when cells were cultured at 26°C instead
of 37°C. Pretreatment with CFTR channel blockers glibenclamide (100 μm) and DPC (100 μm), with hexokinase (0.5 U/mg), and with the purinoceptor antagonist suramin (100 μm), inhibited the forskolin [Ca2+]
i
response. Together, these results demonstrate that once activated, CFTR regulates [Ca2+]
i
by mediating nucleotide release and activating cell surface purinoceptors in normal and CF human airway epithelia.
Received: 3 April 2000/Revised: 30 June 2000 相似文献
125.
Welters HJ Diakogiannaki E Mordue JM Tadayyon M Smith SA Morgan NG 《Apoptosis : an international journal on programmed cell death》2006,11(7):1231-1238
Saturated and mono-unsaturated fatty acids exert differential effects on pancreatic β-cell viability during chronic exposure.
Long chain saturated molecules (e.g. palmitate) are cytotoxic to β-cells and this is associated with caspase activation and
induction of apoptosis. By contrast, mono-unsaturated fatty acids (e.g. palmitoleate) are not toxic and can protect against
the detrimental effects of palmitate. In the present study, we show that the protective actions of palmitoleate in BRIN-BD11
β-cells result in attenuated caspase activation following exposure to palmitate and that a similar response occurs in cells
having elevated levels of cAMP. However, unlike palmitoleate, elevation of cAMP was unable to prevent the cytotoxic actions
of palmitate since it caused a diversion of the pathway of cell death from apoptosis to necrosis. Palmitoleate did not alter
cAMP levels in BRIN-BD11 cells and the results suggest that a change in cAMP is not involved in mediating the protective effects
of this fatty acid. Moreover, they reveal that attenuated caspase activation does not always correlate with altered cell viability
in cultured β-cells and suggest that mono-unsaturated fatty acids control cell viability by regulating a different step in
the apoptotic pathway from that influenced by cAMP. 相似文献
126.
Forskolin is a potent activator of the cyclic AMP-generating system in many tissues. In dog thyroid slices, the enhancement of cyclic AMP level was rapid, sustained in the presence of forskolin, but easily reversible after its withdrawal. Contrary to TSH, forskolin induced little apparent desensitization. Forskolin potentiated the effects of TSH, PGE1 and cholera toxin. However, the forskolin-induced cyclic AMP accumulation was still sensitive to inhibitors of dog thyroid adenylate cyclase such as iodide, norepinephrine and adenosine. As fluoride, but contrary to TSH and PGE1, forskolin stimulated adenylate cyclase in a medium where Mg2+ was replaced by Mn2+. This suggests that in thyroid, as in other tissues, forskolin acts beyond the receptor level but, as it potentiates hormone action and does not impair modulation by inhibitors, it may interact with the nucleotide-binding regulatory proteins. Forskolin mimicked the effect of TSH on iodide organification and secretion. 相似文献
127.
《European journal of cell biology》2023,102(2):151292
Non-Small-Cell Lung Cancer (NSCLC) is considered one of the most frequently diagnosed cancers and the leading cause of cancer-related deaths worldwide. Despite the undoubted therapeutic advances that have occurred in clinical practice over time, due to its high degree in both heterogeneity and resistance, NSCLC remains largely incurable. As a natural cAMP elevating agent, Forskolin has shown anti-cancer properties in different tumor types, thus supposing its possible usage in treating malignancies. In this study, we investigated the Forskolin outcome in H1299 and A549 NSCLC cell lines, either alone or in combination with Paclitaxel. We proved that Forskolin impairs cell growth and migration ability of these cells, concurrently. Albeit with a different extent between H1299 and A549, changes in cell-cycle progression and epithelial-mesenchymal markers were observed in response to Forskolin administration. Interestingly, comparable cell growth impairment was also obtained with the cAMP phosphodiesterase inhibitor IBMX, while the employment of adenylyl cyclase inhibitor SQ22536 counteracted, at least in part, the Forskolin-mediated anticancer effects. Besides as a single agent, we also demonstrated that Forskolin strongly enhances Paclitaxel-induced cytotoxicity, affecting cell death mainly via apoptosis induction. Notably, H89-mediated protein kinase A (PKA) inhibition further deteriorated the combination outcome. Altogether, our data designate Forskolin as a possible anticancer molecule in NSCLC, and recognize the adenylyl cyclase/cAMP axis as one of the pathways involved in. Although achieved at preclinical stage, our findings encourage the design of future studies aimed at further exploring the Forskolin employment in NSCLC treatment. 相似文献
128.
A. J. Kiliaan G. Scholten P. B. Bijlsma K. Dekker J. A. Groot 《Cell and tissue research》1996,285(1):51-56
The transepithelial route for mucosa-to-serosa transport of the tracer macromolecule horseradish peroxidase (HRP; MW 40 kDa)
and modulation of this transport by forskolin and carbachol have been studied in vi-tro in stripped goldfish intestinal epithelium
mounted in Ussing-type chambers. Uptake and transport have been investigated by measuring the HRP flux from the muco-sal to
serosal sides by an enzymatic method and by visualising HRP reaction products in the mucosa with electron-microscopical techniques.
Both the cholinergic agonist carbachol (which is thought to increase intracellular Ca2+ and activate protein kinase C activity) and forskolin (a direct activator of adenylylcyclase) affect the amount of enzymatically
active HRP in the tissue. In control tissue, HRP product is found only within the epithelial cells, the transepithelial flux
reaching a constant value of about 1.5 pmoles/cm2 per h. Carbachol increases the amount of HRP product in the cells, but has no significant effect on the HRP flux compared
with control values. Forskolin decreases the amount of HRP product in the cells; however, in the presence of forskolin, the
lateral intercellular spaces become filled with HRP product. HRP is found in the lamina propria and the transepithelial protein
flux increases more than 2.5-fold. In the presence of forskolin plus carbachol, the results are no different from the control.
It is concluded that carbachol increases the endocytotic uptake of HRP, whereas forskolin inhibits the uptake but increases
the paracellular permeability for HRP in goldfish intestine.
Received: 10 July 1995 / Accepted: 4 February 1996 相似文献
129.
Yasuo Totsuka Mehdi S. Ferdows Thor B. Nielsen James B. Field 《Biochimica et Biophysica Acta (BBA)/General Subjects》1983,756(3):319-327
Forskolin (40 μM) stimulated adenylate cyclase activities of bovine thyroid plasma membranes without pthe addition of guanine nucleotides. GDP had little effect on the forskolin-stimulated adenylate cyclase activity while Gpp[NH]p (0.1–1.0 μM) decreased it. In the presence of TSH (10 mU/0.11), Gpp[NH]p no longer caused inhibition. Forskolin did not affect phosphodiesterase activities of thyroid homogenates. Forskolin (10 μM) rapidly increased cAMP levels in bovine thyroid slices both in the absence and presence of a phosphodiesterase inhibitor. The effect of TSH (50 mU/ml) on cAMP levels was additive or greater than additive to that of forskolin. An initial 2-h incubation of slices with forskolin did not decrease their subsequent cAMP responses to either forskolin and/or TSH while similar treatment of slices with TSH induced desensitization of the cAMP response to TSH, but not to forskolin. Forskolin (10 μM) as well as TSH (50 mU/ml) activated cAMP-dependent protein kinase of slices in the absence of a phosphodiesterase inhibitor. Although forskolin activated the adenylate cyclase cAMP system, it did not stimulate iodide organification or glucose oxidation, effects which have been attributed to cAMP. In fact, forskolin inhibited these parameters and 32P incorporation into phospholipids as well as their stimulation by TSH. These results indicate that an increase in cAMP levels and cAMP-dependent protein kinase activity in thyroid slices may not necessarily reproduce the effects of TSH on the thyroid. 相似文献
130.