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At least 955 records · Page 53Linked to original sources
PubMed2002

Endothelin-induced changes in the physiology of retinal pericytes.

PURPOSE: Pericytes are positioned on the abluminal wall of capillaries and are thought to play a role in regulating retinal blood flow. Although endothelin (ET)-1 is a putative endothelium-pericyte signal, the mechanisms by which this molecule regulates pericyte function remain unclear. Because ion channels play a vital role in the response of pericytes to extracellular signals, this study was undertaken to assess the effects of ET-1 on ionic currents. METHODS: The perforated-patch configuration of the patch-clamp technique was used to monitor whole-cell currents of pericytes located on microvessels freshly isolated from the rat retina. To assay cell-to-cell coupling within retinal microvessels, a gap junction--permeant tracer was loaded through patch pipettes into pericytes and the spreading of the tracer detected by immunohistochemistry. RESULTS: ET-1 acting through ET(A) receptors altered pericyte currents and caused depolarization of the membrane potential. The effects on pericyte currents were dynamic over time. Initially, the nonspecific cation (NSC) and calcium-activated chloride (Cl(Ca)) currents were activated and the adenosine triphosphate (ATP)-sensitive potassium (K(ATP)) current inhibited. Subsequently, by a mechanism sensitive to a protein kinase C (PKC) inhibitor, the NSC, Cl(Ca), and voltage-dependent potassium currents diminished as gap junction pathways closed within the microvessels. CONCLUSIONS: ET-1 regulates pericyte conductances by multiple mechanisms. One process involves a PKC-dependent closure of gap junction pathways resulting in loss of electrotonic input from neighboring cells. Thus, ET-1 not only affects individual microvascular cells, but also regulates the effective size of the multicellular functional units that may serve to control capillary blood flow. This regulation of intercellular communication within pericyte-containing microvessels may be an important, previously unrecognized, action of ET-1.

Alkaloids↗
PubMed2002

Effects of fasting on corticosterone production by zona fasciculata-reticularis cells in ovariectomized rats.

BACKGROUND: To investigate the function and mechanism of fasting on the production of corticosterone in vitro by zona fasciculata-reticularis (ZFR) cells from ovariectomized (OVX) rats. METHODS: Female rats were OVX for 4 days before decapitation. Rats were fed or fasted for 1 day before experiment. ZFR cells from fed and fasted rats were incubated with adrenocorticotropic hormone (ACTH), forskolin, 8-bromo-3',5'-cyclic adenosine monophosphate, SQ22536, nifedipine, chelerythrine chloride, trilostane or steroidogenic precursors at 37 degrees C for either 60 or 30 minutes. Corticosterone, pregnenolone concentrations in spent media, and the intracellular adenosine 3',5'-cyclic monophosphate (cAMP) concentration were determined by radioimmunoassay. The effects of fasting in response to ACTH on the protein expressions of steroidogenic acute regulatory protein (StAR) or cytochrome P450 side-chain cleavage enzyme (P450scc) in ZFR cells were determined by Western blot analysis. RESULTS: The concentration of plasma corticosterone in fasted rats was significantly higher than that in fed rats (P<0.01). One-day fasting significantly increased the responsiveness of ZFR cells to ACTH, forskolin, and precursor-stimulated corticosterone productions and to forskolin-stimulated cAMP accumulation. The corticosterone production was reduced in fasted group when adenylyl cyclase was inhibited by SQ22536. The fasting-enhanced level of corticosterone production in ZFR cells was decreased by the administration of nifedipine but not altered by that of chelerythrine chloride. Fasting significantly increased trilostane-stimulated production of pregnenolone in ZFR cells. The activities of enzymes which converting cholesterol, pregnenolone, progesterone, and deoxycorticosterone to corticosterone and the expressions of StAR in ZFR cells were greater in fasted rats than in fed rats. CONCLUSIONS: This study demonstrated that fasting increased the release of corticosterone and the accumulation of cAMP by rat ZFR cells. The action mediated through enhancing the responsiveness to ACTH stimulation, cAMP cascades and the activity of L-type calcium channels. The activities of steroidogenic enzymes including P450scc, 3beta-hydroxysteroid dehydrogenase, 21-hydroxylase, and 11beta-hydroxylase were all enhanced by the fasting treatment.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMedDate not supplied

Sanguinaria-related leukoplakia: epidemiologic and clinicopathologic features of a recently described entity.

An association between the use of Viadent toothpaste and/or mouthwash and the development of leukoplakia oral mucosal lesions has been described recently. Discontinuing the Viadent products may result in resolution of the leukoplakia, although frequently this is not the case. In order to corroborate the earlier study and to provide further insight regarding the clinical features of this process, a case-control study was conducted. A significant association was seen between the use of Viadent products and the development of oral leukoplakia. Furthermore, leukoplakias affecting sites other than the buccal vestibule also were associated with the use of these products.

Alkaloids↗
PubMed2002

[Effect of a fungal elicitor on levels of sanguinarine and polyphenoloxidase activity in a suspension culture of Papaver somniferum L].

The opium poppy (Papaver somniferum L.) is still a source for isolation of codeine and morphine. Cell cultures from this plant lose their ability to produce morphinans. Their major alkaloid is sanguinarine. The elicitation of the opium poppy cell cultures by fungal preparation lead to a nine-fold increase in the content of sanguinarine. The specific activity of polyphenoloxidase (PPO) was three-times higher in the elicited compared to the nonelicited cells. Two isoforms of PPO (Mr 63 kDa, 41 kDa) were identified in opium poppy cell cultures by PAGE. The number of PPO isoforms was not affected by elicitation. Phenyl-Sepharose CL-4B was used for affinity purification of PPO. In a single purification step the specific activity of PPO was enriched 14-fold.

Alkaloids↗
PubMedDate not supplied

[A role of protein kinase C in signal reactions in outer segments of the bovine retinal rods].

The effect of modulators of protein kinase C activity on Ca2+ translocation in dark-adapted and bleached retinal rod outer segments (ROS) was studied. The activators (1,2-diacyl glycerol and phorbol-12-myristate-13-acetate) and the inhibitor (chelerythrine chloride) of protein kinase C were shown to stimulate and inhibit the ATP-dependent Ca(2+)-uptake in dark-adapted retinal ROS, correspondingly. Apparently, this action is due to the influence of protein kinase C on Ca(2+)-ATPase activity in these vesicular structures. No involvement of modulators of protein kinase C activity on ATP-dependent Ca(2+)-uptake in bleached retinal ROS was found. The influence of protein kinase C on Ca(2+)-release from retinal ROS was observed. It was shown that the activators and inhibitors of protein kinase C increased the efficiency of this process both in dark-adapted and bleached retinal ROS. The mechanisms of action of the protein kinase C activity modulators on the Ca(2+)-uptake and Ca(2+)-release in retinal ROS are discussed.

Adenosine Triphosphate↗
PubMed2002

Differential mechanisms of morphine antinociceptive tolerance revealed in (beta)arrestin-2 knock-out mice.

Morphine induces antinociception by activating mu opioid receptors (muORs) in spinal and supraspinal regions of the CNS. (Beta)arrestin-2 (beta)arr2), a G-protein-coupled receptor-regulating protein, regulates the muOR in vivo. We have shown previously that mice lacking (beta)arr2 experience enhanced morphine-induced analgesia and do not become tolerant to morphine as determined in the hot-plate test, a paradigm that primarily assesses supraspinal pain responsiveness. To determine the general applicability of the (beta)arr2-muOR interaction in other neuronal systems, we have, in the present study, tested (beta)arr2 knock-out ((beta)arr2-KO) mice using the warm water tail-immersion paradigm, which primarily assesses spinal reflexes to painful thermal stimuli. In this test, the (beta)arr2-KO mice have greater basal nociceptive thresholds and markedly enhanced sensitivity to morphine. Interestingly, however, after a delayed onset, they do ultimately develop morphine tolerance, although to a lesser degree than the wild-type (WT) controls. In the (beta)arr2-KO but not WT mice, morphine tolerance can be completely reversed with a low dose of the classical protein kinase C (PKC) inhibitor chelerythrine. These findings provide in vivo evidence that the muOR is differentially regulated in diverse regions of the CNS. Furthermore, although (beta)arr2 appears to be the most prominent and proximal determinant of muOR desensitization and morphine tolerance, in the absence of this mechanism, the contributions of a PKC-dependent regulatory system become readily apparent.

Alkaloids↗
PubMed2000

[Concentration of four alkaloids in the aerial parts of Eomecon chionantha from different mounth in year].

The concentration of four alkaloids (sanguinarine, chelerythrine, protopine and alpha-allocryptopine) in the aerial parts of snowpopy (Eomecon chionantha) collected from April to August in 1996 were determined by capillary electrophoretic method. The results show that the change of contents of alkaloids according to months is similar to that of the underground parts of snowpopy, i.e. the contents of sanguinarine and chelerythrine wrer lower in June than other months; the contents of chelerythrine were higher than that of sanguinarine and alpha-allocryptopine were higher than protopine.

Alkaloids↗
PubMed2001

[RP-HPLC method for determination of protopine in plasma and pharmacokinetics in rats].

AIM: To develop a reversed phase high performance liquid chromatographic method (RP-HPLC) for determination of protopine (Pro) in rat plasma and to investigate the pharmacokinetics of Pro in rats. METHODS: The column was packed with 5 microns C18. The mobile phase (pH 5.6) was a mixture of methanol-water-10% acetic acid (80:20:2). After twice extracted with ether under basic condition, and reextracted with 0.02 mol.L-1 sulfuric acid, protopine in the plasma samples was isolated well. The content of protopine in the plasma sample was measured by UV detector at 285 nm. RESULTS: The lowest limit of detection was 50 ng.mL-1. The intraday and interday precisions were 1.5%-3.0% and 2.1%-6.2%, respectively. The mean recovery was 80.6%-97.6%. A good linear relationship between the peak height and the concentration of protopine in rat plasma was observed. The pharmacokinetics of protopine had been investigated in rats after intravenous administration 10 mg.kg-1. The concentration-time curve of protopine in rat was confirmed to two-compartment open model. The T1/2 alpha, T1/2 beta, Ke, CL, Vd were 0.05 h, 1.85 h, 1.52 h, 6.41 L.h-1 and 17.27 L, respectively. CONCLUSION: This method is suitable for studies on pharmacokinetics of protopine.

Analgesics, Opioid↗
PubMed2003

Quaternary benzo[c]phenanthridine alkaloids as inhibitors of dipeptidyl peptidase IV-like activity baring enzymes in human blood plasma and glioma cell lines.

Quaternary benzo[c]phenanthridine alkaloids (QBA), fagaronine (FA), sanguinarine (SA), chelerythrine (CHE) and the QBA extract from Macleya cordata (EX) exerted differential inhibitory effect on the hydrolytic activity of particular dipeptidyl peptidase (DPP)-like enzyme isolated from human blood plasma and from human and rat glioma cell lines. The low-MW form of DPP-IV-like enzyme activity, corresponding most probably to DPP-8, observed only in glioma cells but not in human plasma, was inhibited preferentially by SA, CHE and EX, and only slightly by FA. The alkaloid inhibitory effect was concentration-dependent in the range 25-150 mM and directly pH-related. In addition, a subtle but consistent inhibition of the intermediate-MW form of DPP-IV-like enzyme activity, ascribed to DPP-IV/CD26, observed only in human plasma and of the attractin (high-MW form of DPP-IV-like enzyme activity, expressed in U87 glioma cells) by the studied alkaloids was observed. We conclude that some of the QBA biological effects could be determined by tissue and cell type specific dipeptidyl peptidase IV-like molecules expression pattern.

Alkaloids↗
PubMed2003

[Effects of chelerythrine on cell proliferation and p27 expression of cardiac fibroblasts modulated by arginine vasopressin].

OBJECTIVE: To study the effects of chelerythrine, a protein kinase C (PKC) inhibitor, on the cell proliferation and p27 expression of cardiac fibroblasts (CFs) modulated by arginine vasopressin (AVP) and to investigate the intracellular signal transduction mechanisms of AVP in CFs. METHODS: The cultured CFs of neonatal Sprague-Dawley rats were divided into 3 groups: AVP group (10(-7) mol/L AVP was added into the culture), chelerythrine group (10(-6) mol/L chelerythrine and 10(-7) mol/L AVP were added into the culture), and control group. MTT assay was used to evaluate the cell proliferation. The cultured cells were collected and propidium iodide was used to label the DNA so as to identify the cell cycle. Specific mouse-versus-rat p27 protein monoclonal antibody and fluorescein isothiocyanate-labeled secondary antibody were added into the cell suspension to label the p27 protein in the cells. Flow cytometry was used to determine the distribution of cell cycles and p27 expression. RESULTS: (1). The A value of CFs measured by MTT assay in AVP + chelerythrine group was 0.32 +/- 0.01, significantly lower than that of the AVP group (0.39 +/- 0.01, P < 0.01). (2). The percentage of CFs in S stage was 4.4% +/- 1.7% in the AVP + chelerythrine group, lower than those of the AVP group (15.5% +/- 1.4%, P < 0.01) and control group (7.5% +/- 1.0%). The PI of CFs was 20.9% +/- 1.2% in the AVP + chelerythrine group, significantly lower than that of the AVP group (31.4% +/- 1.5%, P < 0.01). The PI of the AVP group was significantly lower than that of the control group (26.0% +/- 1.0%, P < 0.01). The percentage of CFs in G(0)/G(1) stage was 79.1% +/- 1.2% in the AVP + 1 chelerythrine group, significantly higher than that in the AVP group (68.6% +/- 1.5%, P < 0.01). The percentage of CFs in G(0)/G(1) stage in the AVP group was significantly lower than that in the control group (74.0% +/- 1.0%, P < 0.01) too. (3). The expression rate of p27 protein was 91.7% +/- 2.2% in the AVP + chelerythrine group, significantly higher than that in the AVP group (63.3% +/- 1.9%, P < 0.01). CONCLUSION: PKC inhibitor remarkably reverses the CFs proliferation and p27 downregulation induced by AVP. It may be involved in the intracellular signal transduction pathway of AVP in CFs.

Alkaloids↗
PubMed2003

Activation of prodeath Bcl-2 family proteins and mitochondrial apoptosis pathway by sanguinarine in immortalized human HaCaT keratinocytes.

Sanguinarine, derived from the root of Sanguinaria canadensis and other poppy fumaria species, possesses strong antimicrobial, anti-inflammatory, and antioxidant properties. We earlier showed that sanguinarine kills human epidermoid carcinoma A431 cells via an induction of apoptosis [N. Ahmad et al., Clin. Cancer Res., 6: 1524-1528, 2000]. In this study, using immortalized human keratinocytes (HaCaT cells), we provide information about mechanism of the antiproliferative effect of sanguinarine. Sanguinarine [0.1 (M-2 (M)] treatment to HaCaT cells was found to inhibit in a dose-dependent manner the cell proliferation and induce apoptosis, as measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and ELISA, respectively. Sanguinarine treatment also resulted in a significant cleavage of poly(ADP-ribose) polymerase in HaCaT cells. Because mitochondrial pathway is critical for the regulation of apoptosis, we studied the involvement and regulation of mitochondrial events in sanguinarine-mediated apoptosis of HaCaT cells. As shown by the immunoblot analysis, our data clearly demonstrated that sanguinarine treatment to HaCaT cells resulted in a dose-dependent (a) increase in the level of Bax with a concomitant decrease in Bcl-2 levels and (b) increase in Bax/Bcl-2 ratio. Sanguinarine also resulted in significant increases in the proapoptotic members of Bcl-2 family proteins, i.e., Bak and Bid. This was accompanied by increase in (a) protein expression of cytochrome c and apoptotic protease-activating factor-1 and (b) activity and protein expression of caspase-3, caspase-7, caspase-8, and caspase-9. Taken together, our data showed the involvement of mitochondrial pathway and Bcl-2 family proteins during sanguinarine-mediated apoptosis of immortalized keratinocytes. We suggest that sanguinarine could be developed as a drug for the management of hyperproliferative skin disorders, including skin cancer.

Alkaloids↗
PubMedDate not supplied

Pituitary adenylate cyclase-activating polypeptide (PACAP)-evoked increase in cyclic AMP production in chick cerebral cortex: lack of a role of the protein kinase C pathway.

Pituitary adenylate cyclase-activating polypeptide 38 (PACAP38) is a potent activator of cyclic AMP formation in the chick brain. The peptide also stimulates inositol phosphates accumulation and protein kinase C (PKC) activity in the chick cerebral cortex. In this work, we analyzed whether PACAP38-induced increase in cyclic AMP production in the chick cerebrum can be modified by a PKC pathway. 4Beta-phorbol 12,13-dibutyrate (4beta-PDB), a PKC activator, did not significantly affect the PACAP38-evoked increase in [3H]cyclic AMP production in [3H]adenine-prelabeled slices of the chick cerebral cortex. Of the tested PKC inhibitors, i.e. chelerythrine, H-7, NPC-15437 and staurosporine, only chelerythrine markedly decreased, in a concentration-dependent manner, the PACAP38-activated cyclic AMP accumulation in the chick cerebrum. These results suggest that (1) the process of cyclic AMP production stimulated by PACAP in the cerebral cortex of chick is not PKC-dependent, and that (2) chelerythrine, a widely used PKC inhibitor, influences the intracellular signaling pathway(s) associated with PACAP receptors in the chick brain in a way not involving PKC.

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