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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The roles of Ca2+ and cyclic nucleotides as secondary, intracellular messengers for exflagellation of Plasmodium berghei and Plasmodium falciparum were investigated. Treatment with Ca2+ antagonists such as TMB-8 (an inhibitor of intracellular Ca2+ release) or W-7 (a calmodulin inhibitor) strongly inhibited exflagellation induced by alkaline medium at pH 8.0 whereas EGTA (a Ca2+ chelator) or nicardipine and nifedipine (Ca2+ channel inhibitors) had no effect. These results may indicate that mobilization of parasites' internal resources of Ca2+ is a prerequisite for exflagellation. Agents which increase cAMP levels did not induce exflagellation at the non-permissive pH of 7.3, and had no significant inhibitory effect at the permissive pH of 8.0. IBMX (cAMP/cGMP-phosphodiesterase inhibitor), however, enhanced exflagellation at pH 7.3, indicating the possibility that cGMP, but not cAMP, may be involved in the induction of exflagellation. Furthermore, cGMP or agents which increase cGMP levels such as nitroprusside (a potent activator of guanylate cyclase), enhanced exflagellation at pH 7.3, whereas N-methyl-hydroxylamine (guanylate cyclase inhibitor) inhibited the exflagellation at pH 8.0. From these results, it may be concluded that the induction of exflagellation requires both Ca2+ mobilization and an increase in cGMP levels.
Mol Biochem Parasitol 1990 Aug
PMID:Possible roles of Ca2+ and cGMP as mediators of the exflagellation of Plasmodium berghei and Plasmodium falciparum. 217 16

The thymidine analog 5-bromodeoxyuridine (BrdU) suppresses pigmentation and tyrosinase activity in Syrian hamster melanoma cells W1-1-1. Studies on the molecular mechanism of suppression of pigmentation indicated that BrdU treatment affects the level of tyrosinase gene transcripts. No detectable tyrosinase message was found by Northern blot analysis in cells cultured in the presence of BrdU at concentrations even as low as 0.2 microM. The level of tyrosinase mRNA was found to reflect the level of pigmentation and tyrosinase activity. Studies with dibutyryl cyclic AMP (cAMP) showed that it inhibited pigment synthesis in W1-1-1 cells. With increasing concentrations of cAMP ranging from 10 microM to 300 microM, pigmentation and tyrosinase activity decreased progressively. This inhibition was found to be associated with a corresponding decrease in the level of tyrosinase mRNA. W1-1-1 cells were found not to respond to melanocyte stimulating hormone (MSH). There was no change in pigmentation, tyrosinase activity, or tyrosinase mRNA level in W1-1-1 cells in the presence of MSH. Similarly, theophylline, a phosphodiesterase inhibitor, had no effect on pigmentation or tyrosinase activity in W1-1-1 cells.
Somat Cell Mol Genet 1990 Nov
PMID:Bromodeoxyuridine- and cyclic AMP-mediated regulation of tyrosinase in Syrian hamster melanoma cells. 217 54

The intermediary role and relative importance of cAMP in follicle-stimulating hormone (FSH) hormonal action were reinvestigated at the level of the rat granulosa cell employing Rp-cAMPS, a novel antagonistic analog of cAMP. This approach may not only provide for direct documentation of cAMP dependence, but may also, by inference, highlight the potential relative importance of other putative intracellular second messenger systems. Initial cell-free validation studies indicated that Rp-cAMPS is capable of effectively competing with cAMP for binding to and activation of the regulatory subunit of the granulosa cell A-kinase holoenzyme. Subsequent whole-cell studies employed cultured rat granulosa cells, the cAMP-phosphodiesterase activity of which was suppressed with ZK62711. Basal progesterone accumulation was relatively low, remaining unaffected by treatment with a maximally effective dose of Rp-cAMPS by itself (10(-3) M). Whereas treatment with FSH (30 ng/ml) resulted in a substantial increase in progesterone accumulation, concurrent treatment with increasing concentrations (10(-6)-10(-3) M) or Rp-cAMPS brought about dose-dependent decrements in the FSH effect with a median effective dose of 1.8 +/- (SE) 0.4 x 10(-5) M and a maximal, but incomplete inhibitory effect of 70 +/- (SE) 6%. Higher concentrations of FSH (greater than or equal to 100 ng/ml) progressively diminished, but did not abolish the Rp-cAMPS blockade. Removal of Rp-cAMPS resulted in progressive resumption of FSH responsiveness suggesting reversibility of action. Significantly, Rp-cAMPS proved highly effective in blocking the action of its agonistic diastereomer Sp-cAMPS. However, Rp-cAMPS was unable to block the action of the lactogenic receptor agonist prolactin, the second messenger of which remains uncertain. Taken together, these findings provide additional direct support to the notion that cAMP may be an intracellular second messenger of FSH. However, to the extent that Rp-cAMPS is incapable of complete neutralization of FSH action, our findings further suggest that cAMP may play a central, albeit non-exclusive role in FSH-supported granulosa cell differentiation and that other putative second messenger systems may also be at play.
Mol Cell Endocrinol 1990 Jul 30
PMID:Blockade of granulosa cell differentiation by an antagonistic analog of adenosine 3',5'-cyclic monophosphate (cAMP): central but non-exclusive intermediary role of cAMP in follicle-stimulating hormone action. 217 13

Platelet aggregation and secretion are associated with a rise in intracellular calcium concentration ([Ca2+]i). Adenosine has been postulated as an endogenous inhibitor of platelet aggregation. The antiaggregatory effects of adenosine are related to activation of adenylate cyclase. We studied the effect of adenosine on the rise in [Ca2+]i and platelet aggregation produced by thrombin. Human platelets were obtained from dextrose/citrate-treated plasma. [Ca2+]i was determined by fluorescence-dye techniques (fura-2). Adenosine inhibited the slope of the first phase of aggregation and the rise in [Ca2+]i produced by thrombin, in a dose-dependent manner. The dose that produced 50% inhibition of both aggregation and the rise in [Ca2+]i was approximately 500 nM. The effects of adenosine on [Ca2+]i were shared by its stable analogs, 5'-N-ethylcarboxamidoadenosine being approximately 10-fold more potent than (-)N6-phenylisopropyladenosine, suggesting that these effects were mediated through adenosine A2 receptors. Furthermore, caffeine antagonized the inhibitory effects of adenosine on platelet aggregation and [Ca2+]i. The effects of adenosine on [Ca2+]i appear to be mediated through a rise in intracellular cAMP, because they were prevented by the adenylate cyclase inhibitor 2',5'-dideoxyadenosine (1 mM) and were potentiated by phosphodiesterase inhibition with papaverine (1 microM). Adenosine also inhibits the rise in [Ca2+]i produced by thrombin in a calcium-free medium, suggesting that adenosine inhibits both calcium influx and the release of calcium from intracellular stores.
Mol Pharmacol 1990 Jun
PMID:Adenosine inhibits the rise in intracellular calcium and platelet aggregation produced by thrombin: evidence that both effects are coupled to adenylate cyclase. 235 5

Iodide inhibits cyclic AMP accumulation in the thyroid by a process which is prevented by inhibition of iodide uptake and of thyroid peroxidase. By a similar process, it also exerts other independent effects such as the enhancement of iodinated protein release. Iodide inhibited the stimulation of adenylate cyclase by prostaglandin E1, cholera toxin and forskolin. The action of iodide was not relieved by phosphodiesterase inhibitors and was not additive with the effect of norepinephrine or adenosine. Iodide did not decrease the cellular level of ATP. The data are compatible with an inhibition of adenylate cyclase beyond the level of the receptor, presumably at the level of the catalytic unit or its interaction with the positive transducing unit NS. The effect of iodide required TSH for its expression but not for its installation. It was decreased under all conditions in which iodide organification was decreased: decreased iodide or increased methimazole concentration, absence of calcium in the medium, etc. However, the relation between iodide binding to proteins and effect was not linear. The effect was not relieved by washing in the absence of iodide and in the presence of perchlorate, but it was partly reversible in the presence of methimazole propylthiouracyl or thiourea. It was not relieved by cooling to 20 degrees C and cytochalasin b, which block stimulated thyroglobulin hydrolysis and iodothyronine release, nor by actinomycin D, cycloheximide, puromycin, mepacrine or indomethacin. The data suggest that iodide binds to a saturable cell component by a reaction which is reversible only in the presence of thiol-containing drugs.
Mol Cell Endocrinol 1985 May
PMID:Further characterization of the iodide inhibitory effect on the cyclic AMP system in dog thyroid slices. 240 38

The putative neuropeptide, molt-inhibiting hormone (MIH), regulates crustacean growth by periodically suppressing the secretion of ecdysteroid molting hormone from peripheral glands (Y-organs). A mediating role for cyclic AMP (cAMP) in MIH action was evaluated with isolated Y-organs of the crab, Cancer antennarius. MIH activity in eyestalk extracts inhibited ecdysteroid secretion but increased cAMP levels dose-dependently in 24-h incubations. The cAMP rise preceded the onset of ecdysteroid suppression. Dibutyryl cAMP, activators of adenylate cyclase (forskolin, choleragen), and an inhibitor of phosphodiesterase (IBMX), but not AMP or cGMP, mimicked the inhibitory action of MIH.
Mol Cell Endocrinol 1985 Sep
PMID:Cyclic AMP mediates the negative regulation of Y-organ ecdysteroid production. 241 11

The relationship between long-term electrical activity and protein phosphorylation was investigated in single, identifiable neurons in the abdominal ganglion of Aplysia californica by the intracellular injection of radiolabeled ATP followed by sodium dodecyl sulfate (SDS) gel electrophoresis. Natural and pharmacological treatments that alter the impulse activity of neurons L6 and R15 for prolonged periods did not appear to affect the phosphorylation of most of the 15 major phosphoproteins examined in these cells. Long-term excitation of L6 induced by the phosphodiesterase inhibitor IBMX correlated with phosphorylation of a 29,000-dalton protein. Long-term inhibition of L6 induced by afterdischarge of peptidergic bag-cell neurons appeared to cause dephosphorylation of a 29,000-dalton protein. Burst augmentation of R15 induced by bag-cell afterdischarge did not cause detectable changes in the phosphorylation of the major proteins we examined. These data are consistent with other studies of neural and nonneural tissues which have found a correlation between activity and the level of phosphorylation of a 29,000-dalton protein.
Cell Mol Neurobiol 1985 Dec
PMID:Activity-related changes in protein phosphorylation in an identified Aplysia neuron. 241 15

The H1-histamine receptor antagonist [3H]mepyramine bound with high affinity (Kd = 3-5 nM) to membranes derived from 1321N1 human astrocytoma cells. The H1-receptor antagonists triprolidine and diphenhydramine inhibited [3H]mepyramine binding with Kj values of 1-5 nM, whereas the Kj of the H2-histamine receptor antagonist cimetidine was greater than 100 microM. Histamine also inhibited [3H]mepyramine binding to 1321N1 cell membranes, and the histamine inhibition curve was shifted to the right and steepened in the presence of 1 microM guanosine 5'-O-(3-thiotriphosphate). Treatment of 1321N1 cells with pertussis toxin had no effect on the capacity of histamine to inhibit [3H]mepyramine binding either in the absence or presence of guanosine 5'-O-(3-thiotriphosphate). Therefore, agonist-occupied histamine receptors in these cells apparently interact with a guanine nucleotide regulatory protein that is not the inhibitory guanine nucleotide regulatory protein of adenylate cyclase. Although adenylate cyclase activity was not affected by histamine in a cell-free preparation, incubation of 1321N1 cells with histamine resulted in an attenuation of cyclic AMP accumulation. Analysis of cyclic AMP degradation in the presence of histamine indicated that the effects of histamine on cyclic AMP accumulation are mediated through activation of phosphodiesterase. This idea was supported by the fact that the phosphodiesterase inhibitor 1-isobutyl 3-methylxanthine blocked attenuation of cyclic AMP accumulation by histamine in a noncompetitive manner. Histamine also markedly increased phosphoinositide breakdown and 45Ca2+ efflux in 1321N1 cells. These histamine-induced effects apparently are mediated through H1-receptors, since triprolidine, but not cimetidine, potently inhibited histamine action. As for histamine interaction with its receptor, pertussis toxin had no effect on histamine-induced phosphoinositide breakdown, 45Ca2+ efflux, or attenuation of cyclic AMP accumulation. Taken together, these data indicate that 1321N1 human astrocytoma cells are a useful model system for the study of H1-histamine receptors and the biochemical responses mediated through these receptors.
Mol Pharmacol 1986 Feb
PMID:H1-histamine receptors on human astrocytoma cells. 241 44

Agonist occupation of muscarinic cholinergic receptors of 1321N1 human astrocytoma cells results in an activation of phosphodiesterase and a resultant 50-75% attenuation of isoproterenol-stimulated cyclic AMP accumulation. The effects of a series of phosphodiesterase inhibitors on muscarinic receptor-mediated inhibition of cyclic AMP accumulation and on the activities of partially purified, soluble phosphodiesterase have been compared to determine which form of phosphodiesterase activity is regulated by muscarinic receptors. The phosphodiesterase inhibitors (50 microM) 1-methyl-3-isobutylxanthine (MIX), 1-methyl-3-isobutyl-7-benzylxanthine (7-BzMIX), 1-methyl-3-isobutyl-8-methoxymethylxanthine (8-MeOMeMIX), and 2-O-propoxyphenyl-8-azapurin-6-one (MB 22948) blocked the effect of muscarinic receptor activation. However, 1-isoamyl-3-isobutylxanthine (IIX) and 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (Ro 20-1724) did not block muscarinic receptor-mediated effects but enhanced isoproterenol-stimulated cyclic AMP accumulation. Three forms of soluble phosphodiesterase activity were resolved by DEAE-cellulose chromatography and sucrose density gradient centrifugation. A calmodulin-stimulated phosphodiesterase activity was inhibited by MIX, 7-BzMIX, 8-MeOMeMIX, and MB 22948 (IC50 values = 1-10 microM) but was not inhibited by IIX and Ro 20-1724. The similar relative capacities of the phosphodiesterase inhibitors for blocking both the muscarinic receptor-mediated attenuation of cyclic AMP accumulation and the calmodulin-stimulated phosphodiesterase activity in vitro suggest that it is this form of enzyme that is regulated by muscarinic receptor stimulation.
Mol Pharmacol 1986 May
PMID:Identification of the phosphodiesterase regulated by muscarinic cholinergic receptors of 1321N1 human astrocytoma cells. 242 35

Transducin, the GTP-binding protein of the retinal light-sensitive phosphodiesterase system, and Gs and Gi, regulatory proteins of the hormone-sensitive adenylate cyclase, are members of a family of guanyl nucleotide-binding proteins termed G proteins that are important in signal transduction. To probe relationships within this family of G proteins, monoclonal antibodies were prepared against the alpha-subunit of bovine transducin (T alpha). Three of four monoclonal antibodies were specific for T alpha and did not cross-react with other G proteins. One, MAB1, cross-reacted strongly with the alpha-subunit of Gi (Gi alpha) purified from rabbit liver and, to a lesser extent, with the alpha-subunit of Go (Go alpha) purified from bovine brain and the proto-oncogene product H-ras p21. All four monoclonal antibodies recognized epitopes on a 23-kDa tryptic peptide fragment of T alpha which is derived from the N-proximal region. The three monoclonal antibodies that recognized only T alpha inhibited rhodopsin-stimulated GTP binding and hydrolysis by transducin, whereas MAB1 had no significant effect in these assays. These studies demonstrate that, within the 23-kDa tryptic peptide of T alpha, there is a domain(s) unique to T alpha that is involved in GTP binding and hydrolysis and another domain which is highly conserved in T alpha and to a lesser extent in other G proteins. Prior studies have identified regions involved in nucleotide binding and hydrolysis that are homologous in all G proteins. The observations reported here are consistent with the conclusion that the G proteins may have in addition unique regions involved in these functions.
Mol Pharmacol 1986 May
PMID:Structural and functional characterization of guanyl nucleotide-binding proteins using monoclonal antibodies to the alpha-subunit of transducin. 242 38


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