Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.4.1 (phosphodiesterase)
18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several aspects of the cyclic 3', 5'-adenosine monophosphate system of rat mammary glands were investigated including effects of stage of pregnancy and lactation upon tissue cyclic 3', 5'-adenosine monophosphate amounts and adenyl cyclase, cyclic 3', 5'-adenosine monophosphate phosphodiesterase, and protein kinase activities. Cyclic 3', 5'-adenosine monophosphate decreased at early lactation, and this decrease coincided with an increase in phosphodiesterase activity. Adenyl cyclase activity remained unchanged from late pregnancy to end of lactation. At late pregnancy, activity of protein kinase was about the same as during lactation indicating that increase in protein kinase activities in the glands precedes increases in activities of other major enzymes and the increase in ribonucleic acids in late pregnancy or early lactation. Epinephrine, prolactin, growth hormone, thyroxine, and prostaglandine caused 60, 80, 140, 200, and 270% increases in adenyl cyclase activity in vitro.
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PMID:Changes in the cyclic 3', 5'-adenosine monophosphate system of rat mammary gland during lactation cycle. 16 62

The ionophore A23187 increased the release of rat growth hormone in the presence of a phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine; a second ionophore X537A inhibited growth hormone release induced by the methylxanthine. A23187 did not alter rat growth hormone release in the absence of 3-isobutyl-1-methylxanthine, but X537A enhanced hormone release in the absence of calcium or in the presence or somatostatin. These findings provide further evidence that both calcium and cyclic AMP are important in the regulation of growth hormone release. Tissue incubated in X537A combined electronlucent vesicles apparently derived from the Golgi apparatus, swollen granules and mitochondria with dense matrices. Tissue incubated in the presence of valinomycin or A23187 did not show altered morphology of either secretory granules or the Golgi complex. Possible mechanisms of these changes are discussed.
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PMID:Modifications in the release of rat growth hormone in vitro and the morphology of rat anterior pituitaries incubated in various ionophores. 17 32

Thyrotropin-releasing hormone (TRH) has 3 effects on clonal strains of rat pituitary cells in culture (GH-cells). Two long-term effects of TRH on GH-cells, which are measurable after 3 h or longer, have been previously reported; these are an increase in prolactin synthesis and a decrease in growth hormone production. We report here that TRH also stimulates the rapid release of stored intracellular prolactin. We have investigated the role of cyclic AMP as a possible mediator of the effects of TRH on GH-cells. Cyclic AMP concentrations are higher in cells treated with TRH compared with paired controls; a maximum difference of greater than 150% of control values is detected at 15 min if the incubation is performed in serum-free medium in the presence of 1 mM theophylline. The concentration of TRH required to give half-maximum increases in both prolactin release and cyclic AMP accumulation is 0.3 nM; half-maximal increases in prolactin synthesis occur at 3 nM TRH. Exogenous cyclic AMP (1 mM) causes only a slight increase in prolactin release; 8-bromo-cyclic AMP and 8-methylthio-cyclic AMP (1 mM) do not cause significant release. Phosphodiesterase inhibitors (0.3 mM theophylline, 0.03 mM isobutyl-methylxanthine) increase prolactin release but their effects on hormone synthesis are more complicated. Isobutylmethylxanthine, 8-bromo-cyclic AMP and 8-methylthio-cyclic AMP (0.4 MM) increase prolactin synthesis, but do not significantly affect growth hormone synthesis. Theophylline increases the synthesis of both hormones. Dibutyryl cyclic AMP (0.5 mM or more) increases prolactin release and both growth hormone and prolactin synthesis, but equivalent amounts of sodium butyrate have the same effects. We conclude that in GH-cells under carefully defined experimental conditions: 1) TRH causes an increase in intracellular cyclic AMP concentrations; 2) the increase in endogenous cyclic AMP and the effects of phosphodiesterase inhibitors are consistent with a model with cyclic AMP as a mediator of the effects of TRH on prolactin release; however, they do not prove this model, because the interpretation of these results depends on assumptions which may not all be valid; and 3) none of the analogs of cyclic AMP or the phosphodiesterase inhibitors tested mimic the decrease in growth hormone production caused by TRH.
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PMID:A possible role of cyclic AMP in mediating the effects of thyrotropin-releasing hormone on prolactin release and on prolactin and growth hormone synthesis in pituitary cells in culture. 17 74

Ovine growth hormone (1 mug/ml) antagonized the lipolytic action of epinephrine (0.25 mug/ml) in segments of adipose tissue obtained from hypophysectomized rats, but a lag period of about 10 min was required. When added simultaneously with epinephrine, growth hormone neither reduced the maximal accumulation of cyclic AMP which occurred at 3 min nor accelerated the return to basal levels. Only when tissues were exposed to epinephrine 15 min after preincubation with growth hormone was cyclic AMP accumulation compromised. Growth hormone also produced a delayed increase of about 20% in the activity of a low Km cyclic nucleotide phosphodiesterase, which might have contributed to the decrease in cyclic AMP accumulation. The increase in phosphodiesterase activity probably did not account for the antilipolytic effect, however, since antilipolysis was evident before the increase in phosphodiesterase activity could be detected. The antilipolytic effects of growth hormone similarly could not be attributed to the decrease in cyclic AMP concentrations, for when added simultaneously with epinephrine the antilipolytic effects did not occur until after the evanescent changes in cyclic AMP had passed. Growth hormone added simultaneously with epinephrine or 30 min later significantly decreased the activity of protein kinase assayed in the absence of exogenous cyclic AMP, but did not change total protein kinase activity as measured in the presence of a saturating concentration of cyclic AMP. This effect of growth hormone was evident as early as 3 min after addition of the hormone and may at least partially account for the antilipolytic effect.
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PMID:Studies on the mechanism of the antilipolytic effects of growth hormone. 18 54

Fluoride-stimulated adenylate cyclase is demonstrated inisolated tumor cells of transplantable rat pituitary tumor MtT-F4 in vitro. The intracellular cyclic adenosine 3':5'-monophosphate is lowered in the cells incubated in the presence of synthetic somatostatin. Contrary to the findings reported for normal pituitary, however, the immunoreactive growth hormone release does not change when either somatostatin or phosphodiesterase inhibitors are present in the incubation medium. The presence of dibutyryl cyclic adenosine 3':5'-monophosphate (5 mM) in the incubation medium does not change the rate of growth hormone release by isolated tumor cells.
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PMID:Effect of somatostatin on growth hormone release by MtT-F4 rat pituitary tumor in vitro. 19 84

The possible involvement of growth hormone (GH) in the regulation of ovarian function in the goldfish was investigated by determining the effects of common carp GH on steroid production by vitellogenic and preovulatory ovarian follicles incubated in vitro. Carp GH acts in a dose-dependent manner to potentiate the actions of common carp gonadotropin (GtH) on the production of 17 beta-estradiol and testosterone by vitellogenic ovarian follicles and the actions of human chorionic gonadotropin (hCG) on testosterone production by preovulatory ovarian follicles. Carp GH alone had no effect on basal steroid secretion by either class of ovarian follicles. Chum salmon GH but not bovine GH also enhanced carp GtH-induced production of 17 beta-estradiol by vitellogenic ovarian follicles. Common carp prolactin had no effects on basal or GtH-stimulated steroid production by vitellogenic or preovulatory ovarian follicles. The actions of carp GH on preovulatory follicles were not apparent when tested with the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine, suggesting that GH may act to enhance either the formation or actions of cAMP. In summary, these data demonstrate that GH has a direct modulatory effect on GtH-stimulated steroid production and suggest that GH may be an important regulator of follicular development in the goldfish.
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PMID:Growth hormone-dependent potentiation of gonadotropin-stimulated steroid production by ovarian follicles of the goldfish. 169 73

Somatostatin (SRIF) reduces growth hormone releasing hormone (GRF)-stimulated growth hormone (GH) release from avian and mammalian adenohypophyseal cells. The present studies examined the intracellular mechanisms mediating SRIF inhibition of GRF-stimulated GH release from chicken pituitary cells. Increases (P less than 0.05) in GH release were observed in the presence of (1) GRF; (2) the adenylyl cyclase stimulator, forskolin; (3) a cAMP analog, 8-bromo-cAMP; (4) the phosphodiesterase inhibitor 3-isobutyl-l-methyl-xanthine (IBMX) combined with GRF; (5) a tumor-promoting phorbol ester and protein kinase C activator, phorbol 12-myristate, 13-acetate (PMA); (6) a diacylglycerol analog, 1,2-dioctanoyl-glycerol (DiC8); and (7) a calcium ionophore, A23187, alone and in combination with PMA. Somatostatin (10 ng/ml) reduced the release of GH stimulated by GRF, forskolin, and 8-bromo cAMP and the GRF-provoked release of GH in the presence of IBMX (P less than 0.05). Somatostatin, however, did not influence GH release in the presence of the protein kinase C activators, PMA or DiC8, or the calcium ionophore A23187. These data suggest that SRIF inhibits GRF-provoked GH release by reducing the ability of the cAMP-protein kinase A but not of the calcium or protein kinase C intracellular message pathways to stimulate GH release.
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PMID:Possible involvement of adenylyl cyclase-cAMP-protein kinase a pathway in somatostatin inhibition of growth hormone release from chicken pituitary cells. 170 26

In pituitary GH1 cells, a rat growth hormone-producing cell line, butyrate elicited a dose-dependent increase in cholera toxin receptors as measured by an increased binding of 125I-labeled cholera toxin to the intact cells. Butyrate did not alter the affinity of cholera toxin binding, the dissociation constant being 0.4 nM for both control and butyrate-treated cells. Despite the increased binding, the cAMP response to cholera toxin was strongly reduced after exposure to butyrate. This reduction was dose-dependent and with butyrate 1--5 mM, intracellular and extracellular (medium) cAMP levels were decreased by more than 70% in cells incubated for 24 h with 1 nM cholera toxin. Forskolin (30 microM) elicited a cAMP response similar to that found with the toxin, and a similar inhibition of cAMP was also found after incubation of GH1 cells with butyrate. Butyrate also affected basal cAMP levels which were reduced by 40--60% in cells cultured for 24--48 h with the fatty acid. In order to study whether butyrate influenced cAMP synthesis and/or cAMP degradation, adenylyl cyclase and phosphodiesterase activities were determined in control cells and in cells incubated for 24 h with cholera toxin or forskolin. Butyrate had a dual effect since, besides activating phosphodiesterase by more than twofold, it also inhibited the cyclase by 40--50% in all groups. The in vitro response of adenylyl cyclase to stimulatory (NaF) and inhibitory (carbachol and adenosine) effectors was also examined. The absolute activity of the cyclase was always 40--50% lower in the cells incubated with butyrate, but the percentage change of activity obtained in butyrate-treated and untreated cells was unaltered. In addition, ADP-ribosylation of the guanine nucleotide stimulatory component of the cyclase (Gs) was not affected in the cells incubated with butyrate. These results suggest that the catalytic (C) subunit of adenylyl cyclase and/or its interaction with the regulatory components might be altered in butyrate-treated GH1 cells. The inhibition of the cAMP response in GH1 cells was accompanied by an inhibition of a biological action of the nucleotide, namely growth hormone (somatotropin) production which is primarily controlled by thyroid hormones in these cells. Forskolin alone did not affect the somatotropin levels but potentiated the growth hormone response to triiodothyronine. Butyrate produced a dose-dependent inhibition of this response, which was totally abolished at concentrations of butyrate higher than 1 mM.
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PMID:Regulation by butyrate of the cAMP response to cholera toxin and forskolin in pituitary GH1 cells. 215 80

The hormonal control of proline transport in pyloric ceca was studied in regard to the effects of cortisol, growth hormone (GH), epinephrine, and 3-isobutyl-1-methylxanthine (IBMX). Cortisol pellets implanted in yearling freshwater (FW) salmon for 2 weeks elevated plasma cortisol levels six times above that of control fish. The maximal influx (Jmax) and the half-saturation constant (Kt) of proline influx were twofold greater in cortisol-treated fish than the values in controls; the apparent passive permeability coefficient (Pa) was significantly reduced in the former group. FW salmon implanted with GH for 2 weeks showed increased body weight gain and a higher Jmax of proline influx compared with that of control fish. GH treatment resulted in a higher Pa of proline influx as well as in a 30% increase in area-specific intestinal dry weight. Thus, GH and cortisol may play a regulatory role in intestinal amino acid absorption during salmon development. The in vitro effects of epinephrine and the phosphodiesterase inhibitor, IBMX, on short-circuit current (Isc) and proline influx in salmon intestine were examined. Epinephrine (10(-6) M) caused a rapid increase in negative Isc (mucosa, ground). Pyloric ceca preincubated with epinephrine for 30 min showed reduced total proline influx compared with influx in paired control tissues. Epinephrine increased and IBMX decreased the Kt of proline influx; IBMX also reduced Jmax. The possible interaction between the effects of epinephrine and IBMX on ion transport and Na+-coupled proline influx are discussed.
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PMID:Hormonal effects on L-proline transport in coho salmon (Oncorhynchus kisutch) intestine. 241 38

Somatomedins-insulin-like growth factors (SM/IGF) are growth hormone (GH) dependent serum growth factors. There is some evidence that IGF inhibit GH release (negative feedback) in 3- to 24-h incubations of cultured rat adenohypophysial cells. We have used acutely dispersed noncultured rat adenohypophysial cells to study the dynamics of IGF on GH secretion. In this system both IGF-I and IGF-II (100 ng/mL) slightly, but significantly, decrease the cumulative GH released by human pancreas growth hormone releasing factor 1-40 (GRF) and the phosphodiesterase inhibitor 3-isobutyl-1-methyl xanthine. The inhibition is small (16%) and usually not statistically significant until 2 h of incubation. The inhibition with IGF is additive to that produced with low concentrations of somatostatin. The IGF also significantly decrease the rate of GH release in all time periods tested (0-1, 1-2, 2-3 h). In addition, the IGF decrease the quantity of [14C]leucine protein eluted at the position of labelled rat GH on Sephadex G75, which would include newly synthesized GH extracted from the cells. Thus we conclude that the decreased GH released may be due to an effect of IGF on both rate of release and on GH synthesis.
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PMID:Insulin-like growth factor inhibition of growth hormone secretion. 242 15


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