calcimycin and phorbol

calcimycin has been researched along with phorbol* in 6 studies

Other Studies

6 other study(ies) available for calcimycin and phorbol

ArticleYear
Tumor-promoting phorbol ester down-regulates the androgen induction of prostate-specific antigen in a human prostatic adenocarcinoma cell line.
    Cancer research, 1992, Mar-15, Volume: 52, Issue:6

    Prostate-specific antigen (PSA) is the most sensitive marker available for monitoring the progression of prostate cancer and response to therapy. In a previous study, we demonstrated tissue-specific expression of PSA glycoprotein and mRNA and its regulation through the androgen receptor. In this study, we examine the effects of protein kinase A (PKA) and protein kinase C (PKC) on the androgen regulation of PSA in a human adenocarcinoma cell line, LNCaP. Northern blot analysis demonstrated that forskolin, an activator of PKA, had no effect on the androgen regulation of PSA. However, the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA), a direct activator of PKC, showed a time- and dose-dependent repression of the androgen regulation of PSA glycoprotein and mRNA. The biologically inactive phorbol ester, 4 alpha-phorbol-12,13-didecanoate, had no effect. Staurosporine, a PKC inhibitor, blocked the TPA-mediated repression of the androgenic stimulation of PSA glycoprotein. In addition, the calcium ionophore, A23187, was able to simulate the actions of TPA, presumably through activation of PKC via calcium mobilization. In summary, the androgenic regulation of PSA protein and mRNA is repressed by tumor-promoting phorbol esters through the PKC pathway. This indicates that the effects of TPA may be secondary to repressed gene transcription or altered mRNA stability. In addition, this study emphasizes that the androgenic regulation of PSA is complex and may involve other extracellular transduction signals.

    Topics: Alkaloids; Antigens, Neoplasm; Biomarkers, Tumor; Calcimycin; Colforsin; Dose-Response Relationship, Drug; Down-Regulation; Humans; Male; Nandrolone; Phorbols; Prostate-Specific Antigen; Prostatic Neoplasms; RNA, Messenger; Staurosporine; Testosterone Congeners; Tetradecanoylphorbol Acetate; Tumor Cells, Cultured

1992
Actions of phorbol esters on levels of cAMP in cholera toxin-treated chief cells from guinea pig stomach.
    Biochimica et biophysica acta, 1992, Apr-30, Volume: 1135, Issue:1

    Agents like carbachol and cholecystokinin (CCK), that activate chief cell phosphoinositidase C, thereby increasing cell calcium concentration, increase cAMP levels in cholera toxin-treated, but not control, gastric chief cells. In the present study, we found that phorbol esters, like PMA, that activate protein kinase C, also cause augmentation of chief cell cAMP levels. The maximal effect with PMA (100 nM) was about 50% of the maximal response with CCK (10 nM) or carbachol (100 microM). Because protein kinase C is a calcium-dependent enzyme, we examined the effect of modulating cell calcium levels with the ionophore A23187. The ionophore alone caused a dose-dependent augmentation of cAMP levels. Adding 100 nM PMA caused an additive response, such that a maximal cAMP response, equal to that seen with 100 microM carbachol, was observed with 30 nM A23187. Carbachol-, A23187-, and PMA-induced augmentation of cAMP levels was progressively reduced by increasing concentrations of calmidazolium, a calmodulin inhibitor. Combination of phorbol esters that activate protein kinase C with ionophores that increase cell calcium mimics the actions of CCK and carbachol on cAMP levels in cholera toxin-treated chief cells.

    Topics: Animals; Calcimycin; Calmodulin; Carbachol; Cholera Toxin; Gastric Mucosa; Guinea Pigs; Imidazoles; In Vitro Techniques; Kinetics; Male; Phorbol 12,13-Dibutyrate; Phorbols; Signal Transduction; Sincalide; Tetradecanoylphorbol Acetate

1992
Na+-dependent elevation of the acidic cell surface pH (microclimate pH) of rat jejunal villus cells induced by cyclic nucleotides and phorbol ester: possible mediators of the regulation of the Na+/H+ antiporter.
    Biochimica et biophysica acta, 1988, Jan-22, Volume: 937, Issue:2

    The effects of cyclic nucleotides and phorbol ester on the acidic cell surface pH of rat jejunal villi were studied by using single-barrelled pH-sensitive microelectrodes. Addition of dibutyryl cAMP (1 mM) to the mucosal bathing solution caused an elevation of the cell surface pH from 6.19 +/- 0.04 (n = 12 measurements from three animals) to 6.53 +/- 0.03 (12) in the presence of Na+ in the medium. However, dibutyryl cAMP had no significant effect in the absence of Na+ and presence of 1 mM amiloride. Dibutyryl cGMP (1 mM) also had an Na+-dependent inhibitory effect on the cell surface pH. A phorbol ester, phorbol 12-myristate 13-acetate, caused an elevation of the cell surface pH only in the presence of Na+ from 6.14 +/- 0.07 (12) to 6.46 +/- 0.08 (12). Phorbol and phorbol 13-acetate, which do not stimulate protein kinase C, were without significant effects. These results suggest that increased levels of the intracellular cyclic nucleotides and activation of protein kinase C raise the acidic cell surface pH by inhibiting the activity of the brush-border Na+/H+ antiporter in the rat jejunal villus cells.

    Topics: Amiloride; Animals; Bucladesine; Calcimycin; Carrier Proteins; Cyclic GMP; Dibutyryl Cyclic GMP; Dinoprostone; Hydrogen-Ion Concentration; Jejunum; Male; Microvilli; Phorbol Esters; Phorbols; Prostaglandins E; Rats; Rats, Inbred Strains; Sodium; Sodium-Hydrogen Exchangers; Tetradecanoylphorbol Acetate; Theophylline

1988
Phorbol ester and neomycin dissociate bradykinin receptor-mediated arachidonic acid release and polyphosphoinositide hydrolysis in Madin-Darby canine kidney cells. Evidence that bradykinin mediates noninterdependent activation of phospholipases A2 and C.
    The Journal of biological chemistry, 1988, Oct-15, Volume: 263, Issue:29

    Many types of peptide hormone and neurotransmitter receptors mediate hydrolysis of phosphoinositides (PI) and arachidonic acid and arachidonic acid metabolite (AA) release, but the relation between these responses is not clearly defined. We have characterized bradykinin (BK)-mediated AA release and PI hydrolysis in clonal Madin-Darby canine kidney cells (MDCK-D1). Both responses occurred over a similar dose range in response to the B1 and B2 receptor agonist, BK, but not in response to the B1 receptor-selective agonist des-Arg-BK. To test whether AA release occurs via a mechanism which is sequential to and dependent upon PI hydrolysis, we used the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), which activates protein kinase C. TPA treatment blocked BK-mediated PI hydrolysis in MDCK-D1 cells, while at the same time and at similar concentrations enhancing BK-mediated AA release. Thus, TPA treatment dissociated BK-mediated AA release from PI hydrolysis. In addition, treatment of MDCK-D1 cells with neomycin blocked BK-mediated hydrolysis of phosphatidylinositol bisphosphate without reducing BK-mediated AA release. BK treatment increased formation of lysophospholipids with a time course in accord with BK-mediated AA release, indicating that at least part of the BK-mediated AA release was likely derived from activation of phospholipase A2. BK-mediated lysophospholipid production was enhanced by pretreatment with TPA, suggesting that the mechanism of AA release before and after treatment with TPA was the same. BK-mediated AA release and lysophospholipid production was dependent on the presence of extracellular calcium, while the enhanced responses to BK in the presence of TPA were not dependent on the presence of extracellular calcium. TPA treatment also enhanced AA release and lysophospholipid production in response to the calcium ionophore A23187. From these data we propose that BK, acting at B2 receptors, promotes AA release in MDCK cells via a mechanism which is 1) independent of polyphosphoinositide hydrolysis by phospholipase C, 2) dependent upon influx of extracellular calcium and activation of phospholipase A2, and 3) enhanced by activation of protein kinase C.

    Topics: Animals; Arachidonic Acids; Bradykinin; Calcimycin; Cell Line; Dogs; Enzyme Activation; Hydrolysis; Kidney; Kinetics; Neomycin; Phorbols; Phosphatidylinositol Phosphates; Phosphatidylinositols; Phospholipases; Phospholipases A; Phospholipases A2; Receptors, Bradykinin; Receptors, Neurotransmitter; Tetradecanoylphorbol Acetate; Type C Phospholipases

1988
Phorbol ester-induced inhibition of cyclic GMP formation mediated by muscarinic receptors in murine neuroblastoma cells.
    The Journal of pharmacology and experimental therapeutics, 1987, Volume: 241, Issue:2

    The effects of phorbol 12-myristate 13-acetate (PMA) on carbamylcholine (CBC)-induced [3H]cyclic GMP formation in mouse neuroblastoma cells (clone N1E-115) were studied. PMA, but not 4 alpha-phorbol, suppressed muscarinic receptor-mediated cyclic GMP responses in a time-dependent and a concentration-dependent fashion with an IC50 of 68.8 +/- 20.2 nM. The inhibitory effects of PMA on CBC-induced cyclic GMP formation were of a mixed competitive and noncompetitive type, being characterized by a depression of maximal cyclic GMP response to CBC and a significant increase in its EC50. PMA also significantly reduced [3H]cyclic GMP formation induced by histamine, without affecting the responses elicited either by sodium azide or the calcium ionophore A23187. Although the inhibitory effects of PMA on CBC-induced cyclic GMP formation were not reversed by washing, these effects were significantly attenuated by H-7 [1-(5-isoquinolinesulfonyl)-2-methylpiperazine], a protein kinase C inhibitor. PMA had no effect on binding of an antagonist ligand to muscarinic receptors, or on the binding characteristics of CBC to these receptors in intact cells. On the other hand, PMA competed for the specific binding of a labeled phorbol ester in intact cells with a potency similar to that of PMA in inhibiting muscarinic receptor-mediated [3H]cyclic GMP responses.

    Topics: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Animals; Calcimycin; Carbachol; Cell Line; Cyclic GMP; Dose-Response Relationship, Drug; Histamine; Isoquinolines; Mice; Neuroblastoma; Phorbol 12,13-Dibutyrate; Phorbol Esters; Phorbols; Piperazines; Receptors, Muscarinic; Tetradecanoylphorbol Acetate

1987
Induction of ornithine decarboxylase in guinea-pig lymphocytes. Synergistic effect of diacylglycerol and calcium.
    European journal of biochemistry, 1985, Feb-15, Volume: 147, Issue:1

    Calmodulin antagonists, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), N-(6-aminohexyl)-1-naphthalenesulfonamide (W-5) and trifluoperazine inhibited ornithine decarboxylase induction in lymphocytes activated with phytohemagglutinin or inophore A23187. W-7, a more potent calmodulin antagonist than W-5, suppressed ornithine decarboxylase induction in a higher extent than did W-5. These results suggest that calmodulin may play an important role in ornithine decarboxylase induction in the activated lymphocytes. However, the extent of ornithine decarboxylase induction was greater in cells pretreated with Clostridium phospholipase C and then incubated with ionophore A23187 than in cells incubated with ionophore A23187 without the pretreatment. Moreover, combined treatment of cells with ionophore A23187 and tumor promotor, phorbol 12-myristate 13-acetate, caused synergistic induction of ornithine decarboxylase activity. These results, taken together, suggest that both activations of Ca2+-activated phospholipid-dependent protein kinase by diacylglycerol and of calmodulin-dependent function resulted from an elevation of cytosolic Ca2+ concentration may operate in the induction of ornithine decarboxylase in the activated lymphocytes.

    Topics: Animals; Calcimycin; Calcium; Calmodulin; Cells, Cultured; Cytosol; Diglycerides; Enzyme Induction; Glycerides; Guinea Pigs; Lymphocytes; Ornithine Decarboxylase; Phorbol Esters; Phorbols; Phytohemagglutinins; Protein Kinase C; Protein Kinases; Type C Phospholipases

1985