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 1,081 records · Page 60Linked to original sources
PubMed1978

[Prevention of ventricular fibrillation with the aid of protopine in animal experiments].

The anti-arrhythmic activity of protopin, quinidine and novocainamide infused intravenously as a preventive and relieving measure was studied in acute experiments on rats with calcium chloride and aconitic arrhythmia. In myocardial fibrillation induced by calcium chloride the contents in the rat heart of adrenalin, noradrenaline, dopa and dopamine were studied by spectrofluorimetry before and after the use of protopin. It was established that in the size of its minimum effective doses which arrest or prevent calcium chloride and aconitic arrhythmias in rats protopin is two to three times more potent than quinidine and novocainamide. The mechanism of the anti-arrhythmic effect of protopin in calcium chloride and aconitic arrhythmias is complex and is due to the suppression of the foci of heterotopic stimulation, decrease in excitability of the myocardial cells and normalization of the catecholamine content in the myocardium.

Alkaloids↗
PubMed1980

Effect of sanguinarine on ventricular refractoriness.

The purpose of this study was to determine the effect of the Na+K+ATPase inhibitor sanguinarine on the refractory period of the porcine ventricle. Measurements of ventricular refractoriness and strength-interval curves were obtained before and after 0.5 to 4.0 mg/kg sanguinarine. The ventricular refractory period was found to be prolonged at all doses studied from a control of 276 +/- 12 msec to 318 +/- 24 msec at 4.0 mg/kg (p < 0.01). The strength-interval curve was shifted to increased values for ventricular refractoriness from 0.5 to 16.0 ma. No depression of arterial pressure or left ventricular dp/dt was observed. This study shows that sanguinarine prolongs ventricular refractoriness. This property may be useful in the treatment of ventricular arrhythmias.

Alkaloids↗
PubMed1993

Correlation between platelet aggregation and dephosphorylation of a 68 kDa protein revealed through the use of putative PKC inhibitors.

The efficacy of two structurally and functionally unrelated protein kinase C (PKC) inhibitors, chelerythrine and calphostin C, was assessed in intact human platelets by studying platelet aggregation in response to stimulation with phorbol 12-myristate 13-acetate (PMA) or the thromboxane-A2 mimetic, U46619. Surprisingly, both inhibitors increased aggregation in response to PMA, but decreased aggregation in response to U46619. To further explore this phenomenon, gel electrophoresis of 32P-labelled proteins from PMA- or U46619-stimulated platelets in the presence and absence of the two putative PKC inhibitors was performed. Although neither chelerythrine nor calphostin C proved to be effective PKC inhibitors in intact human platelets, a strong correlation between the dephosphorylation of a 68 kDa protein and the rate of platelet aggregation was observed. From these results, the indiscriminate use of PKC inhibitors in whole platelets is questioned and attention is drawn to the role of protein dephosphorylation in platelet activation. The 68 kDa protein was the major phosphorylated substrate in resting platelets. Okadaic acid increased phosphorylation of this band, indicating active phosphate group turnover under resting conditions.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1994

Induction of apoptotic DNA fragmentation and cell death in HL-60 human promyelocytic leukemia cells by pharmacological inhibitors of protein kinase C.

The present studies were undertaken to characterize further the potential role of protein kinase C (PKC) in the regulation of apoptosis in HL-60 promyelocytic leukemia cells. The capacity of acute exposure to specific and nonspecific pharmacological inhibitors of PKC to promote apoptotic DNA fragmentation was examined both quantitatively and qualitatively and correlated with effects on cellular differentiation and proliferation. Incubation of HL-60 cells for 6 h with chelerythrine and calphostin C (highly specific inhibitors that act at the regulatory domain) or H7 and gossypol (nonspecific inhibitors that act at the PKC catalytic domain) produced concentration-dependent increases in DNA fragmentation. Induction of DNA fragmentation by chelerythrine, calphostin C, and gossypol was biphasic, resulting in a sharp decline in effect at concentrations above 5 microM, 0.1 microM, and 100 microM, respectively, whereas maximal and more stable effects were observed in response to H7 (100 microM). A 6-h exposure to staurosporine, a nonspecific but potent PKC inhibitor, failed to induce DNA fragmentation at concentrations generally used to achieve maximal inhibition of enzyme activity (e.g., 50 nM) but promoted fragmentation at considerably higher concentrations (e.g., > or = 200 nM). In contrast, 6-h exposures to the nonspecific protein kinase inhibitor hypericin (0.1 to 100 microM) or to the nonspecific inhibitor of protein kinase A, HA1004 (50 microM), were without effect on DNA fragmentation. DNA obtained from cells exposed to chelerythrine (5 microM), calphostin C (100 nM), H7 (50 microM), gossypol (50 microM), and staurosporine (200 nM)--but not hypericin (25 microM)--exhibited clear evidence of internucleosomal DNA cleavage on agarose gel electrophoresis; moreover, these cells exhibited the classical morphological features of apoptosis (cell shrinkage, nuclear condensation, and the formation of apoptotic bodies). All of the PKC inhibitors that induced apoptosis, and one of the inhibitors that did not (hypericin), substantially inhibited HL-60 cell clonogenicity at the concentrations evaluated. None of the agents tested induced cellular maturation as assessed by nonspecific esterase and nitro-blue tetrazolium positivity. DNA fragments obtained from cells exposed to specific and nonspecific PKC inhibitors possessed predominantly 5'-phosphate termini, consistent with the action of a Ca(2+)-/Mg(2+)-dependent endonuclease. Finally, Northern blot analysis revealed that exposure to calphostin C at a concentration that induced apoptosis (100 nM) failed to alter expression of bcl-2, an oncogene known to block apoptosis in both lymphoid and myeloid leukemia cells.(ABSTRACT TRUNCATED AT 400 WORDS)

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