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At least 937 records · Page 52Linked to original sources
PubMed1991

Role of prolactin in growth of the rat mammary tumor MTW9.

The growth of MTW9 mammary tumors exhibits different degrees of responsiveness to ovariectomy, ranging from sensitivity to resistance. This range of response is a function of time elapsing from tumor inoculation until performance of ovariectomy provided that prolactin (PRL) level is kept continuously high. In vivo studies showed that the MTW9 tumors developed by chronic administration of spiramide were sensitive to ovariectomy by 60 days, but they became resistant to ovariectomy by 100 days. However, when spiramide treatment was discontinued after tumor appearance, the tumors were still sensitive to ovariectomy by 100 days. Chromatofocusing (CF) profile of cytosolic estrogen receptors (ER) correlated with the responsiveness to ovariectomy. A 2-peak profile for tumors sensitive to ovariectomy, and only a one-peak profile for tumors resistant to ovariectomy, were seen. Although the prolactin level in rats bearing the tumors was higher than in the normal rats, no correlation between the PRL level and the change in CF profile of ER over time was seen. Also, these changes could not be correlated with the tumor size. In vitro studies showed that incubation of cytosolic ER from a sensitive tumor (2 peaks) with PRL led to a CF profile with only one peak, characteristic of a resistant tumor. Leupeptin, molybdate and phenylmethylsulfonylfluoride (PMSF) could not prevent this transition. The effect was not reproduced by incubation with growth hormone or progesterone. Our data suggest that PRL, either directly or through intermediates, may play a role in changing the response to hormonal therapy of the mammary tumor MTW9.

Animals↗
PubMed1993

The possible involvement of protein phosphatase 1 in thrombin-induced Ca2+ influx of human platelets.

Protein phosphatase 1 is considered to be involved in thrombin-induced platelet activation (Murata et al., Biochem Int 26:327-334, 1992). To clarify the mechanism, we examined the effects of protein phosphatase 1 and 2A inhibitors (calyculin A, tautomycin, okadaic acid) on Ca2+ influx. In the presence of 1 mM Ca2+, thrombin- (0.1 U/ml) induced platelet aggregation and ATP release were inhibited by calyculin A, while this inhibitory effect was abolished in the absence of Ca2+ (EGTA 1 mM). Furthermore, thrombin-induced Mn2+ influx but not intracellular Ca2+ mobilization was inhibited by calyculin A in a dose-related manner. Calyculin A also blocked the ongoing Ca2+ influx when added 3 min after thrombin stimulation. Similar inhibitory effects were observed with okadaic acid and tautomycin in the same potency sequence as the reported one for protein phosphatase 1 (calyculin A > tautomycin > okadaic acid). These results suggest that the anti-platelet effects of phosphatase inhibitors are due to the inhibition of Ca2+ influx and that protein phosphatase 1 plays a key role in the regulation of receptor operated Ca2+ channel of human platelets.

Antifungal Agents↗
PubMed2003

Elucidation of the fragmentation pathways of azaspiracids, using electrospray ionisation, hydrogen/deuterium exchange, and multiple-stage mass spectrometry.

Collision-induced dissociation (CID) mass spectra were generated for azaspiracids using electrospray ionisation (ESI), and hydrogen/deuterium (H/D) exchange was used to ascertain the number and type of replaceable hydrogens in the three predominant azaspiracid toxins. H/D exchange was conveniently achieved using deuterated solvents for liquid chromatography (LC). Using ion-trap mass spectrometry, multiple-stage CID experiments (MS(n)) on the protonated and fully exchanged ions were performed to decipher characteristic fragmentation pathways. The precursor and product ions from azaspiracids lost up to five water molecules from different regions during MS(n) experiments and it was possible to distinguish between the water losses from different molecular regions. These studies confirmed that the first water-loss ion in the spectra of azaspiracids resulted from dehydration at the vicinal diol at C20-C21. Five MS dissociation pathways were identified that resulted from fragmentation of the carbon skeleton of azaspiracids producing nitrogen-containing ions. Two pathways, involving cleavage of the E-ring and C27-C28, gave ions that were found in all azaspiracids. Three pathways, A-ring, C-ring and C19-C20 cleavages, were useful for distinguishing between azaspiracid analogues. The same product ions from backbone fragmentation were also observed using hybrid quadrupole time-of-flight mass spectrometry (QqTOFMS). The fragmentation of the A-ring was the most facile and was exploited in the development of LC/MS(n) methods for the analysis of azaspiracids.

Animals↗
PubMed2006

Unexpected inhibitory regulation of glutamate release from rat cerebrocortical nerve terminals by presynaptic 5-hydroxytryptamine-2A receptors.

Presynaptic 5-HT(2A) receptor modulation of glutamate release from rat cerebrocortical nerve terminals (synaptosomes) was investigated by using the 5-HT(2A/2C) receptor agonist (+/-)-1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane (DOI). DOI potently inhibited 4-aminopyridine (4AP)-evoked glutamate release. Involvement of presynaptic 5-HT(2A) receptors in this modulation of 4AP-evoked release was confirmed by blockade of the DOI-mediated inhibition by the 5-HT(2A) receptor antagonist ketanserin but not by the 5-HT(2C) receptor antagonist RS102221. Inhibition of glutamate release by DOI was associated with a reduction of 4AP-evoked depolarization and downstream elevation of cytoplasmic free calcium concentration ([Ca(2+)](C)) mediated via P/Q- and N-type voltage-dependent Ca(2+) channels (VDCCs). In contrast to the DOI effect on 4AP-evoked release, the agonist had no effect on high external [K(+)] (30 mM)-induced (KCl) stimulation of VDCCs or glutamate release. Likewise, release mediated by direct Ca(2+) entry with Ca(2+) ionophore (ionomycin) or by hypertonic sucrose was unaffected by DOI. Mechanistically, DOI modulation of 4AP-evoked glutamate release appeared to involve a phospholipase C/protein kinase C signaling cascade, insofar as pretreatment of synaptosomes with the phospholipase C inhibitor U73122 or protein kinase C inhibitors Ro320432 or GF109203X all effectively occluded the inhibitory effect of the agonist. Together, these results suggest that presynaptic 5-HT(2A) receptors present on glutamatergic terminals effect an unexpected depression of glutamate release by negatively modulating nerve terminal excitability and downstream VDCC activation through a signaling cascade involving phospholipase C/protein kinase C. These observations invoke presynaptic inhibitory 5-HT(2A) receptor function as a potential target for drugs to mitigate the effects of excessive glutamatergic transmission.

Amphetamines↗
PubMed1997

Growth hormone secretagogue increases muscle strength during remobilization after canine hindlimb immobilization.

Twenty-two beagles were divided into two equal groups, and the right hindlimb of each animal was immobilized at 105 degrees of knee flexion by external fixation. After 10 weeks of fixation, the device was removed, allowing free mobility for the following 5 weeks. Each day throughout the 15 weeks, one group received a growth hormone secretagogue (treatment) at a dose of 5 mg/kg, and the other received a lactose placebo (control). At weeks 0, 10, and 15, strength as indicated by maximum isometric extension torque was measured in the right hindlimb, biopsies of the vastus lateralis muscle were taken, and the dogs were weighed. Weekly blood samples were analyzed for insulin-like growth factor-1, blood urea nitrogen, and creatine phosphokinase. Between weeks 0 and 10, tetanic torque declined by about 60% (p < 0.001) in both groups, with no significant difference between the groups (p > 0.7). Between weeks 10 and 15, tetanic torque in the treated group increased by 0.81 Nm; this was significantly greater than the increase of 0.25 Nm in the placebo group (p < 0.05). The diameters of slow (type-1) and fast (type-2) fibers measured from the vastus lateralis muscle followed the same trend. At all time points, fiber diameter correlated strongly with torque; this argues against nonmuscular causes such as nerve injury for strength loss. The mean levels of insulin-like growth factor-1 increased 100% by week 4 in the treated group and remained elevated by about 60% throughout the experiment. Levels of insulin-like growth factor-1 in the placebo group decreased 30% within week 1 and remained depressed throughout the experiment. Our interpretation of these data suggests that the growth hormone secretagogue elevated levels of serum insulin-like growth factor-1, which in turn increased the size and strength of the quadriceps muscle during remobilization. These data may ultimately have therapeutic application to humans during rehabilitation after prolonged inactivity.

Animals↗
PubMed1975

Fluorescence reactions of fluorescamine with levodopa and its derivatives: fluorescence assay of 3-methoxy-4-hydroxyphenylalanine in levodopa dosage forms.

A simple fluorometric method for the quantitation of 3-methoxy-4-hydroxyphenylalanine, either alone or in the presence of levodopa, is presented. Fluorescence is developed by reaction with fluorescamine. The interactions of this reagent with levodopa and a number of its derivatives under various experimental conditions were studied. Negligible fluorescence was obtained with levodopa, dopamine, levodopa benzyl ester, and 6-hydroxydopamine.

Chemical Phenomena↗
PubMed1975

Specific TLC tissue residue determination of sulfadiazine following fluorescamine derivatization.

A spectrodensitometric method for the direct determination of sulfadiazine at the tissue residue level (0.1 ppm) is based upon the measurement of the fluorescence of a sulfadiazine-fluorescamine derivative formed directly on a TLC plate by dipping it into a fluorescamine solution. The linear dynamic range for the assay is about 150 from 200 to 0.2 ng, the lower limit of sensitivity. Recoveries from various spiked tissues including milk, eggs, liver, kidneys, muscle, skin, and fat varied with the tissue type but were reproducible. The assay technique has also been used for the assay of sulfamethoxazole and has been explored for use in specifically assaying sulfonamide mixtures.

Animals↗