Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Benzophenanthridines”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,099 records · Page 61Linked to original sources
PubMed1994

Involvement of cytoplasmic calcium and protein kinases in the regulation of atrial natriuretic factor secretion by contraction rate and endothelin.

To characterize the effects of the cellular events associated with contraction on atrial natriuretic factor (ANF) secretion, primary neonatal rat atrial myocytes were electrically paced to contract while being monitored for ANF release, cytoplasmic calcium, phosphoinositide hydrolysis, and protein kinase C activation. Similar measurements were also carried out in the presence of endothelin-1 (ET) for comparison of contraction-related and hormone-stimulated ANF secretion. Pacing (6-8 Hz) immediately increased ANF secretion by 3-5-fold and the time-averaged cytoplasmic calcium concentration (as monitored with indo-1 fluorescence) varied with pace frequency in a similar manner, suggesting that cytoplasmic calcium may play a key role in pace-induced ANF secretion. Furthermore, nifedipine and ryanodine, which inhibited the contractile calcium transients, inhibited pace-induced ANF release, whereas Bay K 8644 increased both the calcium transients and ANF secretion. Pace-induced ANF release was also completely inhibited by KN-62, a specific inhibitor of Ca2+/calmodulin-dependent protein kinase II (CaMK) but was not inhibited by chelerythrine, a protein kinase C-selective inhibitor. Pace-induced ANF release averaged 40% of that elicited by ET which is known to require both PKC and CaMK for maximal effects on ANF secretion. The effects of pacing and ET on ANF secretion were approximately additive. In contrast to pacing, ET strongly stimulated phosphoinositide hydrolysis, activated PKC, and did not increase cytoplasmic calcium. Thus, regulation of ANF secretion by contraction rate depends primarily on the contractile calcium transients and CaMK and is independent of PKC.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1994

Stimulation of protein phosphatase-1 activity by phorbol esters. Evaluation of the regulatory role of protein kinase C in insulin action.

In this study, we examined the role of insulin, protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) cascade in activation of protein phosphatase-1 (PP-1) by using three complementary approaches. First, differentiated L6 cells were acutely exposed to 12-O-tetradecanoylphorbol-13-acetate (TPA, 400 nM) to activate PKC. In these cells, TPA caused 32% stimulation of PP-1 activity. The PP-1 stimulation by TPA was comparable to stimulation by insulin (t1/2 = 1 min and EC50 = 5 nM) with a maximum effect in 5 min. The effects of insulin and TPA were not additive. Insulin and TPA also stimulated MAPK (> 2-fold increase over basal, with myelin basic protein as a substrate). ML-9, a myosin light chain kinase inhibitor, blocked the effects of insulin and TPA on both MAPK and PP-1 activation. In the second approach, PKC was down-regulated by chronic treatment with TPA. In these cells subsequent effects of insulin on MAPK and PP-1 activation were blocked, without an effect on basal enzyme levels. In the third approach, two selective inhibitors of PKC, calphostin and chelerythrine chloride, were used to inhibit PKC. These inhibitors completely prevented insulin and TPA stimulation of MAPK and PP-1 and blocked insulin-induced translocation of PKC to the plasma membranes. We conclude that PKC plays an important role in insulin stimulation of PP-1 via the activation of MAPK cascade.

Alkaloids↗
PubMed1995

1H NMR investigation of the interaction of berberine and sanguinarine with DNA.

Interaction of the alkaloids, berberine and sanguinarine with calf thymus DNA has been studied by 1H NMR. All proton resonances of the two compounds have been assigned using 2D-COSY, NOESY and ROESY spectra. Berberine has been found to partially intercalate into DNA, while sanguinarine shows normal intercalation and also binds more firmly to DNA. The NMR experiments indicate that sanguinarine is more potent than berberine in its activity.

Alkaloids↗
PubMed1995

Noxious thermal and chemical stimulation induce increases in 3H-phorbol 12,13-dibutyrate binding in spinal cord dorsal horn as well as persistent pain and hyperalgesia, which is reduced by inhibition of protein kinase C.

We have previously suggested that protein kinase C (PKC) contributes to persistent pain in the formalin test. This study compared the effects of pharmacological inhibition of PKC with either GF 109203X or chelerythrine on persistent pain following noxious chemical stimulation with its effects on mechanical hyperalgesia, which develops in the hindpaw contralateral to an injury produced by noxious thermal stimulation. Furthermore, we have assessed changes in membrane-associated PKC in spinal cord in response to both noxious chemical and thermal stimulation. Nociceptive responses, to a hindpaw injection of 50 microliters of 2.5% formalin, and flexion reflex thresholds, to mechanical stimulation (Randall-Selitto test) in the hindpaw contralateral to a thermal injury (15 sec immersion in water at 55 degrees C), were assessed following intrathecal injection of PKC inhibitors (GF 109203X or chelerythrine). Changes in the levels of membrane-associated PKC, as assayed by quantitative autoradiography of the specific binding of 3H-phorbol-12,13-dibutyrate (3H-PDBu) in spinal cord sections, were assessed in rats after noxious chemical (50 microliters of 5.0% formalin) and noxious thermal (90 sec immersion in water at 55 degrees C) stimulation. Inhibitors of PKC (GF 109203X, chelerythrine), produced significant reductions of nociceptive responses to 2.5% formalin, as well as a significant reduction in the mechanical hyperalgesia in the hindpaw contralateral to a thermal injury. In addition, both noxious chemical and thermal stimulation produced significant increases in specific 3H-PDBu binding in the dorsal horn of the lumbar spinal cord, likely reflecting alterations in membrane-associated PKC. The results provide both pharmacological and anatomical evidence that persistent pain produced by chemical stimulation with formalin and mechanical hyperalgesia in the hindpaw contralateral to a thermal injury are influenced by the translocation and activation of PKC in spinal cord dorsal horn neurons.

Alkaloids↗
PubMed1995

Ischaemic preconditioning is protein kinase C dependent but not through stimulation of alpha adrenergic or adenosine receptors in the isolated rat heart.

OBJECTIVE: The aim was (1) to clarify whether alpha adrenoceptor and adenosine receptor stimulation is involved in the anti-infarct effect of ischaemic preconditioning in the rat heart, and (2) to test the hypothesis that signal transduction through membrane bound protein kinase C is essential for the protection. METHODS: Isolated, buffer perfused rat hearts were subjected to 30 min of regional ischaemia and 120 min of reperfusion. The risk zone was determined by fluorescent particles, and infarct size was determined by staining with triphenyltetrazolium chloride. RESULTS: Ischaemic preconditioning with three cycles of 5 min ischaemia plus 5 min of reperfusion significantly reduced infarct size as compared to non-preconditioned group [4.5(SEM 0.6)% of the risk zone v 45.5(5.7)%, P < 0.001]. Blockade of alpha adrenoceptors alone and simultaneous blockade of alpha adrenoceptors with phenoxybenzamine (10 microM) and adenosine receptors with sulphophenyltheophylline (100 microM) did not prevent the protective effect of ischaemic preconditioning [infarct size = 2.4(0.4) and 5.6(1.9)% respectively, NS v the non-treated preconditioned group]. Blocking either the membrane binding of protein kinase C with polymyxin B (1 microM) or direct inhibition of protein kinase C activity with chelerythrine (2 microM) completely abolished the infarct size reducing effect of ischaemic preconditioning [32.4(3.3)% and 48.2(4.0)% respectively, P < 0.005 v non-treated preconditioned group: NS v the non-preconditioned group]. CONCLUSIONS: In the rat heart infarct model the protective effect of ischaemic preconditioning is not mediated through stimulation of alpha adrenoceptors alone or the combined stimulation of alpha adrenergic and adenosine receptors, and it is dependent on activation of membrane bound protein kinase C.

Alkaloids↗
PubMed1994

[Effect of protopine on rabbit platelet function].

Protopine (Pro) inhibited dose-dependently rabbit platelet aggregation induced by ADP, arachidonic acid (AA), collagen, or aggregoserpentin of Trimeresurus mucrosquamatus venom (TMVA) in vitro. Their IC50 were 25.3, 30.5, 46.9, 33.4 mumol.L-1, respectively. Pro 10, 20 mg.kg-1 iv also inhibited the platelet aggregation induced by these inducers. The effects (maximal at 5 min) lasted 1 h. By using fluorophotometry and RIA, it was seen that Pro suppressed the release of 5-HT from platelets during aggregation induced by collagen, AA, or TMVM in vitro. Pro did not block the formation of thromboxane A2 during aggregation induced by AA and did not increase the content of cAMP in rabbit platelet, but increased the content of cGMP in rabbit platelets. The antiplatelet effect of Pro may be related to an increase cGMP in rabbit platelets and the suppression of the release of the active substances from platelets.

Alkaloids↗
PubMedDate not supplied

Interleukin-13 is a monocyte chemoattractant.

Recombinant human IL-13 is chemotactic for purified human peripheral blood monocytes Cell migration is stimulated with a typical bell-shaped concentration curve and is maximal at 10 ng/ml. Migration is the result of chemotaxis, and not chemokinesis, as shown by checkerboard experiments. The chemotactic activity of IL-13 on monocytes is not inhibited by preincubation of the cells with pertussis toxin but is diminished by preincubation with protein kinase inhibitors. The related cytokine, IL-4, also stimulates migration of monocytes in the Boyden chamber assays at concentrations similar to those effective for IL-13. Human IL-13 is capable of attracting rabbit peripheral blood monocytes at those concentrations active on human monocytes. On the other hand, no neutrophil migration was induced by IL-13, even at 1 microM concentrations.

Alkaloids↗
PubMed1994

Pathways of heat shock protein 28 phosphorylation by TNF in human fibroblasts.

Treatment of human diploid FS-4 fibroblasts with TNF or IL-1 led to a rapid increase in the phosphorylation of a approximately 28-kDa protein. Increased phosphorylation was seen after 5 min of TNF treatment, it reached a plateau between 10 and 30 min, and decreased thereafter. Immunoprecipitation with specific antibodies identified the 28-kDa protein as a member of the family of small heat shock proteins (Hsp28). Treatment of cells with different kinase inhibitors (staurosporine, H7, H8, HA-1004, or chelerythrine chloride) failed to inhibit TNF-induced Hsp28 phosphorylation, suggesting that neither protein kinase C nor other common protein kinases were involved. Treatment of FS-4 cells with sodium arsenite led to a very strong increase in the phosphorylation of Hsp28 demonstrable after 5 min and persisting for at least 4 h. Tyrosine phosphorylation of pp42 and pp44 MAP kinases was increased by TNF treatment, whereas arsenite produced a modest increase in tyrosine phosphorylation of pp44 while decreasing that of pp42 MAP kinase. The finding that sodium arsenite strongly increased Hsp28 phosphorylation, together with the resistance of TNF-induced phosphorylation to kinase inhibitors, supports the notion that increased serine phosphorylation of Hsp28 in this system involves inhibition of protein phosphatase activity.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1994

Epidemic dropsy in Trans Yamuma areas of Delhi and U.P.

Thirty patients of epidemic dropsy from seven families scattered in different areas of East Delhi and UP were studied. The age group of the affected individuals varied from 2 years to 55 years. Argemone oil contamination was found in mustard oil used for cooking. Sanguinarine was detected in all suspected oil samples. Pitting edema of legs was the most consistent feature present in all cases. Other prominent features like local erythema and tenderness were present in 80% and 70% cases, respectively. In contrast to earlier epidemics, two striking features were presence of persistent tachycardia without any pyrexia in all the cases and absence of any ocular problems. There was one death due to congestive heart failure and partial recovery in all others in a 2 months follow up.

Adolescent↗
PubMed1993

Opioid, calcium, and adrenergic receptor involvement in protopine analgesia.

The analgesic effect of protopine (Pro), an alkaloid isolated from Papaveraceae, was confirmed by tail-pinch and hot-plate tests when given sc 10-40 mg.kg-1, and 20-40 mg.kg-1 inhibited the spontaneous movements of mice. Pro 40 mg.kg-1 increased the sleeping rate, prolonged the sleeping duration, and shortened the sleeping latency in mice hypnotized by ip pentobarbital sodium 30 mg.kg-1. Pro 10-40 mg.kg-1 did not affect the inflammatory reaction induced by xylene and egg white. An icv injection of Pro 20-200 micrograms/mouse showed a remarkable analgesic effect in mice. The icv pretreatment of naloxone 2 micrograms blocked the analgesic effect completely. CaCl2 40 micrograms/mouse (ICV) or methotrexate 10 mg.kg-1 (ip), an agonist of Ca2+ channel, showed a complete blockade of the analgesia, while nifedipine 100 mg.kg-1(po), a blocker of Ca2+ channel, enhanced the analgesic effect. The ip pretreatment of reserpine 4 mg.kg-1 reduced the Pro analgesia. Phentolamine 10 mg.kg-1(ip), an alpha-adrenergic blocker, tended to weaken the analgesia, but propranolol 10 mg.kg-1(ip), a beta-blocker, did not affect it. These results suggest that Pro displays its analgesic effect mainly through the opioid and calcium systems and partly through the adrenergic mechanism.

Alkaloids↗
PubMed1993

Antiseptic activity of some antidental plaque chemicals on Streptococcus mutans biofilms.

S. mutans is one of the bacterial species involved in the initiation of cariogenic dental plaque. In situ, antiseptic activity evaluation of dental plaque chemicals is fairly difficult. A dynamic biofilm model of S. mutans on Tygon support is suitable for the quantification of antiseptic activity and the comparison of commercial chemical formulations, submitted or not to the french standards and Pharmacopea. Some of these chemicals, especially quaternary ammonia solutions, do not reduce living bacteria counts by 10E5 as AFNOR specifies. In the case of dental plaque, antiseptic activity is probably not the only relevant parameter: biofilm dissociation is rather more relevant because the dead or living bacteria adhere to the teeth, favouring the establishment of a new active biofilm. Two proceedings can be followed: support surface can be modified, or bacteria exopolymers synthesis can be inhibited to prevent cell adherence; the disruption of the biofilm glycocalyx can be achieved with enzymes or surfactants.

Alkaloids↗
PubMed1993

Inhibition of the calcium store-operated calcium entry pathway by chemotactic peptide and by phorbol ester develops gradually and independently along differentiation of HL60 cells.

N-formyl-methionyl-leucyl-phenylalanine (fMLP) inhibited transiently the entry of Ca2+ and Mn2+ induced by emptying with thapsigargin the Ca2+ stores of HL60 cells differentiated toward granulocytes. Phorbol 12,13-dibutyrate (PDB) produced a permanent inhibition of this store-operated Ca2+ entry pathway (SOCP), suggesting that inhibition was due to protein phosphorylation mediated by protein kinase C (PKC). Inhibition by PDB was prevented by the PKC inhibitors staurosporin and chelerythrine. Inhibition by fMLP was prevented by chelerythrine but only partially by staurosporin. The characteristics of the inhibition were similar to those reported in human neutrophils (Montero, M., Alvarez, J., and García-Sancho, J. (1993) J. Biol. Chem. 268, 13055-13061). Neither fMLP nor PDB inhibited significantly SOCP in undifferentiated HL60 cells. Single-cell [Ca2+]i measurements at different stages of differentiation showed that inhibition by fMLP and PDB developed independently, suggesting different inhibitory mechanisms. The simplest explanation would be that inhibition by fMLP takes place through activation of a protein kinase distinct from PKC and that the PDB-activated PKC isoform necessary to phosphorylate and inhibit SOCP is expressed only along differentiation. Additionally, inhibition by both fMLP and PDB developed gradually. At intermediate stages of differentiation, PDB was able to produce a partial and maintained inhibition and fMLP a partial and short-lived inhibition of SOCP.

Alkaloids↗
PubMed1993

Quantitative morphological assessment of erythroblastic differentiation induced, in vitro, in human K562 leukemic cells.

K562 human leukemia cell line undergoes in vitro terminal differentiation towards the erythroid pathway following treatments with appropriate chemical agents including aclacinomycin, fagaronine and hemin. These three drugs induced a different expression of phenotypic and functional characters associated with differentiation. The morphological characteristics of the differentiation sequences elicited by these agents were evaluated by image analysis using a SAMBA 200 cell image processor. Multivariate statistical analyses of morphological data revealed that only aclacinomycin was able to induce significant modifications of the morphological parameters similar to those observed during the maturation of normal bone-marrow erythroblastic cells. These data correlate with the higher inductive potency of aclacinomycin as compared to hemin or fagaronine and suggest that quantitative cytology may be a useful adjunct to conventional tests for the selection of new drugs with differentiating potential.

Aclarubicin↗
PubMed1993

Clinical efficacy of dentifrices in the control of calculus, plaque, and gingivitis.

Several dentifrices are available in the market for the control of calculus, plaque, and gingivitis. The anticalculus activity of the pyrophosphate dentifrice formulation has been convincingly demonstrated. Recently, dentifrices containing 0.3% triclosan and 2.0% Gantrez have been shown to possess some anticalculus activity, in addition to their antiplaque and antigingivitis properties. Similarly, sequential application of sanguinarine-containing dentifrice with a brush, followed by a rinse of 30 to 60 seconds, also provides sustained antiplaque and antigingivitis effects. However, other dentifrices have had much less convincing clinical results. It is therefore important for dentists to interpret the therapeutic claims of various antiplaque and antigingivitis dentifrices cautiously before recommending these products to patients.

Alkaloids↗
PubMed1993

Myocardial alpha-thrombin receptor activation induces hypertrophy and increases atrial natriuretic factor gene expression.

The protease, alpha-thrombin (alpha Th), affects myocardial cell contractility, a feature common among agents that induce hypertrophy. However, it is not known whether cardiac myocytes possess alpha Th receptors (alpha Th-R), or if long term treatment with alpha Th can enhance growth and gene expression. In the present study primary neonatal rat ventricular myocytes expressed a 3.6-kilobase mRNA species that hybridized with a rat alpha Th-R-specific probe. After 48 h, alpha Th induced hypertrophy, sarcomeric organization, and enhanced atrial natriuretic factor (ANF) expression, all of which were blocked by the alpha Th-selective protease inhibitor, D-Phe-Pro-Arg-chloromethyl ketone. The alpha Th-R agonist peptide, SFLLRNPND, was a potent activator of ANF expression, however, the non-agonist, FLLRNPND, was inactive. Transfection experiments showed the enhancement of ANF expression by alpha Th to be transcriptional. The abilities of alpha Th to induce myocyte hypertrophy and to augment ANF transcription and peptide production were inhibited by the protein kinase C inhibitor, chelerythrine, and by the tyrosine kinase inhibitor, tyrphostin. Thus, myocardial cell alpha Th-Rs are stimulated by the specific proteolytic actions of alpha Th, and pathways involving both protein kinase C and protein tyrosine kinases are required for subsequent hypertrophy and ANF expression. Further, these findings suggest a new role for extracellular proteases as regulators of myocardial cell gene expression and growth.

Alkaloids↗
PubMed1993

Mouthrinses in the prevention and treatment of periodontal disease.

Although the ideal topical antimicrobial does not exist, some marketed products possess many of the desirable characteristics of such an agent. Antimicrobial agents from a number of different chemical categories are being evaluated continuously. Recent clinical trials evaluating the effectiveness of chlorhexidine, stannous fluoride, prebrushing rinses, phenolic compounds, cetylpyridinium chloride, and new agents such as triclosan are described. Other trials involving special patient groups such as the elderly, mentally handicapped, and orthodontic patients, are discussed. Recent articles on alternative roles for topical antimicrobials are also identified.

Adult↗