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)

When added to primary cultures of adult turtle (Chrysemys) brain, dibutyryl cyclic AMP increases estrogen yields from [3H]testosterone in a dose- and time-dependent manner, although rat FSH, rat LH, and dibutyryl cyclic GMP are relatively ineffective. A phosphodiesterase inhibitor (MIX) by itself increases estrogen yields from the substrate and potentiates the response to dibutyryl cyclic AMP.
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PMID:Aromatization is cyclic AMP-dependent in cultured brain cells. 616 76

The FSH secretion-inhibiting action of inhibin in vitro under basal conditions and also in the presence of LH-RH is suppressed by the addition of MIX, a phosphodiesterase inhibitor. In the presence of LH-RH, inhibin reduces significantly the intracellular level of cAMP in isolated pituitary cells. In contrast, the simultaneous addition of MIX and inhibin raises the cAMP level, and this stimulation is comparable to the increase observed when MIX is added alone. These observations suggest that one mode of action of inhibin could be mediated by a reduction in cAMP within the pituitary gonadotropic cell.
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PMID:[Intracellular mechanism for the action of inhibin on the secretion of the follicular-stimulating hormone and luteinizing hormone induced by LH-RH in vitro]. 616 43

Short-term (4 h) incubation of collagenase-dispersed Leydig cells from adult rats in the presence of an LHRH agonist caused a 2-3-fold stimulation (P less than 0.001) of testosterone production. This effect was dose-dependent and as little as 5 x 10(-11) M LHRH agonist caused significant stimulation whilst maximal effects were achieved with 10(-9) M concentrations. Stimulation of steroidogenesis by LHRH agonist was prevented by addition of an antiserum specific for the peptide, but was exaggerated in the presence of the phosphodiesterase inhibitor MIX, suggesting the involvement of cyclic AMP in the response of the Leydig cells to the agonist. Native LHRH caused a similar degree of stimulation of testosterone secretion to LHRH agonist but concentrations 1000 times greater than those of the agonist were required to achieve this, a finding consistent with the known affinities of these 2 peptides for the Leydig cell LHRH-receptor. The addition of LHRH agonist also enhanced (P less than 0.001) testosterone secretion by adult rat Leydig cells in response to hCG or dibutyryl cyclic AMP, and this effect was still evident in the presence of maximally-stimulating concentrations of these factors. LHRH agonist also stimulated testosterone secretion by Leydig cells from immature rats, but this effect differed from that in the adult in being of smaller magnitude and being restricted to effects on basal secretion or secretion elicited by low concentrations of hCG. These results show for the first time (a) that LHRH and its agonists can exert effects on Leydig cell steroidogenesis during short-term incubation, and (b) that these effects are stimulatory, which contrasts with the inhibitory effects reported after long-term (2-3 days) exposure of Leydig cells to LHRH agonists in vivo and in vitro. The availability of this simple and rapid measure of a biological action of LHRH on the Leydig cell should enable its precise mode of action to be determined, and should throw light on the physiological role of endogenously produced testicular 'LHRH'.
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PMID:Stimulatory effect of LHRH and its agonists on Leydig cell steroidogenesis in vitro. 617 69

In mouse parotid acini both cholinergic and beta-adrenergic agonists increased intracellular levels of cyclic-GMP (c-GMP) as well as amylase release. The derivative of c-GMP, 8-bromo-c-GMP, mimicked the effects of cholinergic and beta-adrenergic stimulation on amylase release. Nitroprusside (NP), hydroxylamine (HA) and sodium azide (NaA) increased c-GMP levels and also enhanced amylase release in a dose-dependent manner; cyclic-AMP (c-AMP) levels were not affected. The phosphodiesterase inhibitor 3-isobutyl-1-methyl-xanthine (MIX) enhanced the effects of carbachol on both c-GMP accumulation and amylase release. These results suggest that c-GMP may mediate the actions of cholinergic agonists and at least partially mediate the actions of beta-adrenergic agonists on mouse parotid enzyme release.
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PMID:Does cyclic GMP mediate amylase release from mouse parotid acini? 618 89

We have studied the effect of agents known to stimulate adenylate cyclase on spontaneous meiotic resumption in vitro by mouse oocytes. We have found that cholera toxin (CT) (up to 1 microM) and prostaglandin E1 (PGE1) (up to 160 microM) are not able to prevent meiotic resumption, but a clear dose-dependent delay in meiosis resumption was observed during the first 3 h of incubation in medium containing CT or PGE1. The effect became clearer when a small concentration of isobutylmethylxanthine (MIX) (1 microM) was added to the medium. We have also measured the cAMP content of the oocyte: the basal content is 2.1 fmol; this value drops to 0.9 fmol during a 2-h culture period. The decrease is partially prevented if CT is present in the incubation medium, while total cAMP content increases to 3.1 fmol in the presence of 1 mM MIX. The results suggest that isolated mouse oocytes contain toxin and prostaglandin sensitive adenylate cyclase and also an active phosphodiesterase system.
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PMID:Meiotic resumption and intracellular cAMP levels in mouse oocytes treated with compounds which act on cAMP metabolism. 618 21

Incubation of intact platelets with prostaglandins (PGE1 and PGI2) and phosphodiesterase inhibitors (1-methyl-3-isobutylxanthine, indomethacin, dipyridamol) lead to activation of cAMP phosphodiesterase. The activation was rapid (maximal within 30 s) and stable after removal of agents and homogenization of platelets. The activation remained after DEAE-Sepharose chromatography. The effect of the two types of agents on phosphodiesterase activity was more than additive and activation did not alter the nonlinear kinetic behavior of phosphodiesterase. The mechanism of the ex vivo stimulation is unknown at the present time, however, it does not seem to be due to cellular redistribution of the enzyme. The results suggest that activation of a cAMP-dependent protein kinase is an intermediate step. The ex vivo stimulation is regulated by a calcium-dependent process, since addition of Ca2+ ions and ionophore A23187 to Ca2+ depleted platelets abolished the ex vivo stimulation by PGE1 and MIX.
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PMID:Rapid activation of cAMP phosphodiesterase in rat platelets. 619 98

The development of responsiveness to prostaglandin E2 (PGE2), FSH, LH, and [Bu]2cAMP was examined in whole ovaries isolated from neonatal Sprague-Dawley rats on days 0 (birth), 2, 4, or 6 postpartum. Pairs of ovaries were incubated with these stimuli in the absence or presence of 3-isobutyl-1-methyl xanthine (MIX), a potent phosphodiesterase inhibitor, and accumulations in the medium of cAMP, androstenedione, and estradiol were measured. PGE2 stimulated marked cAMP accumulation on day 0 whereas similar responses to FSH and LH did not develop until days 2 and 4, respectively. No cAMP accumulation was detectable in the absence of MIX. Ovaries gradually acquired the ability to produce both cAMP and steroids in response to FSH and LH over the first postnatal week. No steroid accumulation was measurable in incubations conducted on days 0 or 2; however, steroidogenesis was stimulable in day-4 ovaries by (Bu)2cAMP. PGE2, FSH, and LH also stimulated steroid accumulation on day 4, but only when MIX was present in the incubation, suggesting that high levels of endogenous cAMP can also lead to steroid production. By day 6, all stimuli elicited steroid accumulation in a dose-dependent fashion. MIX potentiated the responses to lower doses of these stimuli but not to the higher doses at this age. In the absence of MIX, LH was approximately 100 times more potent than FSH in stimulating steroid production; however, the two gonadotropins were nearly equipotent in this regard when MIX was present in the incubation. These results support the notion that a cAMP-sensitive steroidogenic apparatus is present in the rat ovary as early as the fourth day postpartum. Because of the marked effects of MIX on gonadotropin-induced steroidogenesis, it may be that modulation of phosphodiesterase activity is one way by which steroidogenesis is regulated in the neonatal rat ovary.
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PMID:Interactions of a phosphodiesterase inhibitor, 3-isobutyl-1-methyl xanthine, with prostaglandin E2, follicle-stimulating hormone, luteinizing hormone, and dibutyryl cyclic 3',5'-adenosine monophosphate (cAMP) in cAMP and steroid production by neonatal rat ovaries in vitro. 620 25

The effect of forskolin (an adenyl cyclase activator) and 1-methyl-3-isobutylxanthine (MIX, a phosphodiesterase inhibitor) on granulosa cell steroidogenesis and LH receptor formation was studied in vitro. Granulosa cells from immature hypophysectomized, estrogen-treated rats were cultured for 2-3 days in androstenedione-supplemented media in the absence or presence of FSH or forskolin (10(-7)-10(-4) M). Some cultures were also treated with forskolin with or without MIX (0.125-1.0 mM) or theophylline (1.25-10 mM). Forskolin (3 X 10(-6)-10(-4) M) stimulated the production of estrogen, progesterone, 20 alpha-hydroxypregn-4-en-3-one (20 alpha-OH-P) and cAMP in a dose-related manner to levels similar to or higher than that elicited by FSH alone. Similarly, forskolin and FSH both increased LH/hCG receptor content in cultured granulosa cells, although forskolin was only 50% as effective as FSH. Treatment with MIX alone increased basal levels of cAMP, accompanied by elevations of estrogen and progestin biosynthesis without affecting LH/hCG receptor content. In contrast, theophylline treatment only increased cAMP and progestin accumulation. Furthermore, MIX potentiated the stimulatory effects of forskolin and FSH on cAMP and progestin production. In contrast, MIX inhibited FSH- and forskolin-stimulated estrogen production. Thus, activation of adenyl cyclase and inhibition of cAMP breakdown in the cultured rat granulosa cells enhance steroidogenesis and LH receptor formation, reinforcing the concept that cAMP is a (but may not be the only) second messenger in the hormonal regulation of granulosa cell differentiation.
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PMID:Forskolin and phosphodiesterase inhibitors stimulate rat granulosa cell differentiation. 620 17

The mesangial cell is a glomerular cell type with smooth muscle-like (contractile) properties. The responses evoked in cultured mesangial cells by catecholamines were examined in the presence or absence of prostaglandin E2 (PGE2) with or without a phosphodiesterase inhibitor. Exposure to 10(-4) M norepinephrine, epinephrine, or isoproterenol elevated intracellular cyclic AMP (cAMP) levels in mesangial cells (25th to 30th passages) nearly threefold. If isobutylmethylxanthine (MIX) was also included, the hormones caused marked further increases in cAMP (after a 20-min incubation, control with MIX, 64.2 +/- 5.2 pmoles/mg protein; 10(-4) M norepinephrine, 4266 +/- 284 pmoles/mg protein; 10(-4) M epinephrine, 5812 +/- 173 pmoles/mg protein; and 10(-4) M isoproterenol, 3136 +/- 114 pmoles/mg protein). Under both of these circumstances (that is, catecholamines with or without MIX) greater than 50% of the cells underwent a change in shape (that is, had a round cell body with long, thin tapered processes). The cAMP and shape change response was independent of extracellular calcium ions and appeared to be due to beta-adrenergic stimulation. Isoproterenol with MIX stimulated an alteration in morphology and cAMP production at concentrations of 10(-4) M to 10(-9) M. Within 10 min following beta-adrenergic stimulation (10(-4) M isoproterenol plus MIX) cAMP was maximum; at this time a shape change was first evident. Eighty-five to one hundred percent of the cells had undergone a shape change by 40 min. Dibutyryl cAMP (10(-3) M) also induced a shape change in cultured mesangial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cyclic AMP-associated shape change in mesangial cells and its reversal by prostaglandin E2. 620 73

Dispersed bovine placental cells (fetal cotyledon and maternal caruncle) were shown to synthesize progesterone. To determine if their steroidogenic activity could be modulated by a cyclic nucleotide-mediated process, we added luteinizing hormone, 8-bromoadenosine 3',5'-monophosphate, 8-bromoguanosine 3',5'-monophosphate, adenosine, or cholera toxin to dispersed cells from placentomes of 100-283 days gestational age and examined progesterone synthesis during 3-to 16-hr incubation periods. Net progesterone production, defined as the amount of progesterone released in excess of the zero-time cellular progesterone content, was determined by using a specific RIA. None of these agents significantly affected progesterone synthesis. In contrast, the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (MIX; 0.2-0.5 mM) caused a marked increase in progesterone formation. In time course studies it was found that MIX produced a 5-fold increase in progesterone production in 16 hr, with steroid production increasing linearly during this time. MIX also increased the conversion of exogenous pregnenolone to progesterone by placental cells. In view of the failure of cyclic nucleotide analogues and activators of adenylate cyclase to stimulate steroidogenesis, it was necessary to consider other modes of action of MIX. Since MIX is known to affect intracellular calcium translocation, we examined the effects of the calcium ionophore A23187 on progesterone formation. This drug enhanced progesterone formation and augmented the stimulatory effects of MIX. The stimulatory action of A23187 was not affected by cyclic nucleotide analogues. Our data suggest that progesterone synthesis in the bovine placentome is calcium dependent and cyclic nucleotide independent.
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PMID:Calcium-dependent, cyclic nucleotide-independent steroidogenesis in the bovine placenta. 620 49


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