Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A somatic cell genetic approach was used to study the role of cyclic nucleotides in adrenal steroidogenesis. 8-Bromoadenosine 3',5'-monophosphate (8BrcAMP) stimulated steroidogenesis (K'd=0.1 mM) in cultured mouse adrenocortical tumor cells (Clone Y1). In addition, 8BrcAMP inhibited Y1 cell growth and caused Y1 cell monolayers to assume a rounded morphology. As a consequence, 8BrcAMP (at concentrations greater than or equal to 0.4 mM) reduced the relative plating efficiency of Y1 cells to less than 10(-5). Y1 cells were mutagenized with ethyl methanesulfonate (300 microgram/ml) and grown in the presence of 0.4 mM 8BrcAMP. A surviving colony (8BrcAMPr-1) was shown to be resistant to growth inhibition (relative plating efficiency at 1.0 mM 8BrcAMP=50 percent)) and to morphological changes induced by 8BrcAMP. 8BrcAMPr-1 cells had diminished steroidogenic responses to cyclic nucleotides and to ACTH (less than or equal to 33 percent of maximum). In 8BrcAMP(R)-1 cells, adenylate cyclase activity remained responsive to ACTH, and cyclic AMP phosphodiesterase activity was not increased. These data suggest that 8BrcAMPr-1 cells are defective at a point common to cyclic AMP action on growth, morphology and steroidogenesis. The associated decrease in responsiveness of the steroidogenic pathway to ACTH suggests that ACTH-regulated steroidogenesis is via a cyclic nucleotide-mediated mechanism.
Mol Cell Endocrinol 1977 Aug
PMID:Isolation of mutant adrenocortical tumor cells resistant to cyclic nucleotides. 20 May 6

Tritiated salmon calcitonin was prepared by methylation of the free amino groups using tritiated sodium borohydride as precursor. Specific radioactivity was measured in competitive inhibition studies with specific anticalcitonin antibodies or tubular membranes as binding sites for calcitonin. The value observed, approx. 4 Ci/mmol, corresponded to methylation of one third of the available N-H bonds. Tritiated calcitonin prepared in this way retained full biological activity as assessed in vitro by stimulation of adenylate cyclase and in vivo by rat bioassay. Tritiated calcitonin specifically bound to isolated renal cells and nonspecific binding did not exceed 10% of total binding. Equilibrium was obtained after 15 min incubation. The hormone-receptor complex could be dissociated in the presence of an excess of unlabelled calcitonin. This data shows that tritiated calcitonin can be used in metabolic and receptor studies.
Mol Cell Endocrinol 1977 Sep
PMID:Biological and immunological properties of tritiated salmon calcitonin. 20 May 9

The release of 131I-labeled thyroxine (T4) from isolated hog thyroid cells was increased 1.5--2-fold by thyrotropin (TSH). Dibutyryl cyclic AMP failed to reproduce this TSH action. In this in vitro system another cell activity, T4 synthesis, was stimulated in an essentially identical fashion by TSH and dibutyryl cyclic AMP (time course of action, dose-response relationship). 3-Isobutyl-1-methylxanthine (IBMX), 0.5 mM, did not alter the basal [131I]T4 release whereas it enhanced the [131I]T4 synthesis. TSH, 60 MU/ml, increased the intracellular cyclic AMP concentration 3-4-fold. Chlorpromazine (5 X 10(-4)M) abolished the TSH stimulation of cyclic AMP accumulation but did not alter the TSH-induced increase in [131I]T4 secretion. It is concluded that the TSH action on [131I]T4 secretion by isolated thyroid cells is not mediated by the adenylate cyclase-cylic AMP system.
Mol Cell Endocrinol 1977 Nov
PMID:Thyroxine secretion by isolated hog thyroid cells: a cyclic AMP independent pathway. 20 15

Isolated pituitary cells prepared from adrenalectomized rats secrete ACTH in response to CRF, and this response is inhibited by corticosterone. Both the stimulation of release by CRF and the inhibition of release by corticosterone are antagonized by cordycepin (3'-deoxyadenosine). Inhibition of CRF-stimulated secretion by cordycepin is apparently not related to inhibition of RNA synthesis, since high doses of actinomycin D do not affect ACTH secretion. More likely, cordycepin's inhibition of secretion stems from its inhibition of adenylate cyclase activity. Inhibition of corticosterone action by cordycepin is qualitatively similar to that previously reported actinomycin D. This effect of both drugs is probably due to inhibition of RNA synthesis. Significantly, a low dose of cordycepin has a greater inhibitory effect on corticosterone action than on total cellular RNA synthesis. Cordycepin is reported to preferentially inhibit messenger RNA synthesis, and low dose preferentially inhibits appearance of cytoplasmic RNA in pituitary cells. These data suggest that corticosterone-induced RNA is a cytoplasmic (messenger) RNA.
Mol Cell Endocrinol 1978 Jan
PMID:Effect of cordycepin on CRF stimulation and steroid inhibition of ACTH secretion by rat pituitary cells. 20 1

The regulation of catabolite repression of beta-galactosidase has been studied in Escherichia coli mutants deleted for the adenyl cyclase gene (cya delta), and thus unable to synthesize cyclic AMP. It has been found that, provided a second mutation occurs either in the crp gene coding for the catabolite gene activator protein (CAP) or in the Lactose region, these mutants exhibit catabolite repression. If the catabolite repression seen in the mutant strains corresponds to the mechanism operating in wild-type cells the results would suggest that the intracellular concentration of cyclic AMP cannot be the unique regulator of catabolite repression.
Mol Gen Genet 1978 Jun 01
PMID:Catabolite repression in Escherichia coli mutants lacking cyclic AMP. 20 9

Purified bovine pituitary plasma membranes possess two specific LH-RH binding sites. The high affinity site (2.5 X 10(9) l/mol) has low capacity (9 X 10(-15) mol/mg membrane protein) while the low affinity site 6.1 X 10(5) l/mol) has a much higher capacity (1.1 X 10(-10) mol/mg). Specific LH-RH binding to plasma membranes is increased 8.5-fold during purification from homogenate whilst adenylate cyclase activity is enriched 7--8-fold. Distribution of specific LH-RH binding to sucrose density gradient interface fractions parallels that of adenylate cyclase activity. Mg2+ and Ca2+ inhibit specific [125I]LH-RH binding at micromolar concentrations. Synthetic LH-RH, up to 250 microgram/ml, failed to stimulate adenylase cyclase activity of the purified bovine membranes. Using a crude 10,800 g rat pituitary membrane preparation, LH-RH similarly failed to activate adenylate cyclase even in the presence of guanyl nucleotides. These data confirm the presence of LH-RH receptor sites on pituitary plasma membranes and suggest that LH-RH-induced gonadotrophin release may be mediated by mechanisms other than activation of adenylate cyclase.
Mol Cell Endocrinol 1978 Jun
PMID:LH-RH binding to purified pituitary plasma membranes: absence of adenylate cyclase activation. 21 61

Studies of hormone-induced 'desensitization' in the luteinized rat ovary show that changes in receptor number and adenylate cyclase at the cell surface result in an altered biological effect of luteinizing hormone on progesterone production. The sensitivity of these effects to changes in gonadotropin levels suggests that receptor turnover or processing is involved in the normal mechanism of hormone action.
Mol Cell Endocrinol
PMID:Receptor regulation and target cell responses: studies in the ovarian luteal cell. 21 62

1. The effects of phenol and phenyl glucuronide on the responses of normal rat brain adenyl cyclase to noradrenaline and dopamine have been investigated. Neurotransmitter responses have also been examined in brains from uraemic and normal rats. 2. A depressive effect of phenol on the adenosine 3' :5' -cyclic monophosphate response of the neostriatum to dopamine was shown to be completely abolished if the toxin was present in the conjugated form; the response of the cortex to noradrenaline was stimulated by the presence of phenyl glucuronide, even though the unconjugated form had no effect. 3. The uraemic state in the rat also resulted in a depression of the neostriatum response to dopamine, yet an enhancement of the cortical response to noradrenaline. 4. The action of phenols of the brain is relevant to hepatic and uraemic coma.
Clin Sci Mol Med 1978 Sep
PMID:Effect of unconjugated and conjugated phenol and uraemia on the synthesis of adenosine 3' :5' -cyclic monophosphate in rat brain homogenates. 21 46

Rates of synthesis of cyclic 3',5'-adenosine monophosphate (cAMP) were measured in cultures of Escherichia coli aerating without a carbon source. This technique provides a representative measure of adenylate cyclase activity in the absence of inhibition caused by transport of the carbon source. Adenylate cyclase activity was found to vary more than 20-fold depending on the carbon source that had been available during growth. Synthesis of cAMP in cells aerating in the absence of the carbon source was highest when cells had been grown with glucose or fructose which inhibit adenylate cyclase activity severely. Synthesis of cAMP was much lower when cells had been grown with glycerol or succinate which cause only minimal inhibition of the activity. The variation in cAMP synthesis due to different carbon sources requires a functional cAMP receptor protein (CRP). Crp- mutants synthesize cAMP at comparable rates regardless of the carbon source that afforded growth. A novel mutant of E. coli having a CRP no longer dependent on cAMP has been isolated and characterized. Adenylate cyclase activity in this mutant no longer responds normally to variations in the carbon source.
Mol Gen Genet 1978 Sep 20
PMID:The cyclic 3',5'-adenosine monophosphate receptor protein and regulation of cyclic 3',5'-adenosine monophosphate synthesis in Escherichia coli. 21 2

1. The effects of adrenalectomy on the adenylate cyclase--adenosine 3':5'-cyclic monophosphate (cyclic AMP) system of rat renal medulla were examined to evaluate the mechanism of the impaired water diuresis in glucocorticoid deficiency. 2. Concentrations of cyclic AMP in medullary tubules from adrenalectomized rats were significantly higher than in the tubules from control animals both in the presence and absence of antidiuretic hormone. 3. This abnormality was corrected by the treatment in vivo of the adrenalectomized rats with dexamethasone, but addition of this drug to the incubation medium did not abolish the differences in cyclic AMP between tubules from adrenalectomized and normal rats. 4. The activity of adenylate cyclase or cyclic AMP phosphodiesterase in vitro was not affected by adrenalectomy. 5. In glucocorticoid deficiency, the concentration of cyclic AMP in medullary tubules is increased both with and without antidiuretic hormone. This abnormality may render medullary tubules more permeable to water and may underlie the impaired water diuresis in glucocorticoid deficiency.
Clin Sci Mol Med 1978 May
PMID:Effects of glucocorticoid deficiency on renal medullary cyclic adenosine monophosphate of rats. 21 86


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