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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenosine 3',5'-cyclic monophosphate (cAMP) elevation in cultured rat mesangial cells causes urokinase-dependent adhesion loss, stress-fiber fragmentation, and shape change. Thrombin cleaves single-chain urokinase (scu-PA), causing its inactivation, but not two-chain u-PA [tcu-plasminogen activator (PA)] or tissue-type PA. We tested the ability of thrombin to inhibit the effects of cAMP elevation in mesangial cells and inactivate cell-associated scu-PA. In an assay of trypsin-sensitive adhesion, 65.9% of control cells and 5.5% of cells treated with isoproterenol + methylisobutylxanthine (IM) remained adherent. In the presence of 0.01, 0.1, 1.0, and 10.0 unit/ml thrombin, 20.9, 46.6, 50.4, and 53.3%, respectively, of IM-treated cells remained attached. Thrombin also inhibited stress-fiber fragmentation and shape change. The effects of thrombin were blocked by hirudin or antithrombin III plus heparin. Direct zymography in gels containing gelatin and plasminogen revealed loss of a closely spaced pair of PA bands with thrombin treatment (1.0 unit/ml). Hirudin blocked the loss. alpha-Thrombin inactivated by diisopropyl fluorophosphate neither inhibited shape change nor caused loss of the PA bands; however, gamma-thrombin was nearly as active as native alpha-thrombin in both regards. Pretreatment of the cells with as little as 1.0 unit/ml thrombin for 1.0 min caused marked inhibition of shape change and near total loss of the slower migrating u-PA band (of the doublet). The faster migrating band was inhibited less. The results indicate that the slower migrating band represents scu-PA; the nature of the faster migrating band is less certain. Thrombin reversed the adhesion loss and shape change caused by 8-(4-chlorophenylthio)-cAMP and MIX. Thus physiological concentrations of thrombin rapidly inactivate mesangial cell scu-PA and inhibit and reverse cAMP-stimulated adhesion loss and shape change.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of mesangial cell adhesion and shape by thrombin. 165 8

F9 teratocarcinoma stem cells differentiate into parietal endoderm-like cells when given retinoic acid (RA) and dibutyryl cyclic adenosine monophosphate (DB-cAMP). It is generally accepted that the stem cells are resistant to the action of cAMP alone and need to be primed by RA in order to respond to cAMP. In this report, we demonstrate that F9 stem cells differentiate into parietal endoderm-like cells in the absence of exogenous RA when treated with cholera toxin and 1-methyl,3-isobutyl xanthine (CT/MIX) or 8-bromo-cAMP/MIX (8B2-cAMP/MIX). Cells treated with CT/MIX or 8B2-cAMP/MIX were morphologically similar to parietal endoderm-like cells, produced high amounts of plasminogen activator, and synthesized both type IV collagen and laminin mRNA. Conversely, markers made in abundance by stem cells such as stage-specific embryonic antigen (SSEA-1) and an mRNA species of 6.8 kb (pST6-135) were markedly reduced in CT/MIX-treated cells. To prove that cAMP alone could induce differentiation Lipidex-1000, a hydrophobic gel, was used to remove 80-90% of the endogenous serum retinoids. F9 cells grown in this retinoid-depleted serum and treated with 8B2-cAMP/MIX differentiated to parietal endoderm-like cells as shown by both dramatic changes in morphology and induction of type IV collagen mRNA. Our results indicate that the differentiation of F9 to parietal endoderm-like cells can be induced by increased intracellular cAMP and is not strictly dependent on the addition of RA.
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PMID:Cyclic adenosine monophosphate-mediated induction of F9 teratocarcinoma differentiation in the absence of retinoic acid. 169 26

Pre-incubation of rat Sertoli cells with concentrations of follicle-stimulating hormone (FSH) too low to stimulate plasminogen activator (PA) secretion, provoked an inhibition of its subsequent stimulation by an effective dose of the hormone. A kinetic study of this desensitization was performed using equine FSH (which exhibits prolonged stimulation of PA secretion) and porcine FSH (which like all other FSH tested, provokes a transient response). Low non-stimulating concentrations of both hormones were shown to inhibit the subsequent PA response to each of them. Desensitization of rat Sertoli cells by low (non-stimulating) concentrations of FSH did not modify the typical time course (transient or prolonged) of PA secretion under subsequent stimulation by porcine or equine FSH, respectively. Only the intensity of the response to each hormone was dramatically reduced. Besides, the induction of desensitization by these non-stimulating concentrations of FSH was shown to be very rapid (10-15 min). The precise mechanism of this desensitization is not yet clear but its abolishment by the cyclic nucleotide phosphodiesterase (PDE) inhibitor MIX is consistent with the hypothesis that activation of PDE occurs at lower FSH concentration than adenylate cyclase activation.
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PMID:Homologous desensitization of rat Sertoli cells by non-stimulating concentrations of follicle-stimulating hormone. 295 41

To elucidate the possible role of plasminogen activator (PA) in spermatogenesis and spermiation in mammals, we studied the hormonal regulation of PA secretion in cultured rat and mouse seminiferous tubules during defined stages of spermatogenesis. Results indicated that: (1) under basal conditions, segments of rat seminiferous tubules released primarily urokinase-type PA (uPA) at all stages of the cycle. The highest level of PA secretion occurred at stages VIIab, VIIcd and VIII. FSH, 8-bromo cyclic AMP and forskolin (FK) stimulated PA secretion, predominantly tissue-type PA (tPA). (2) In contrast, mouse seminiferous tubules secreted only tPA under basal conditions. In the presence of 50 microM MIX, seminiferous tubules at stages VII and VIII secreted higher levels of both types of PA than at the other stages. Both tPA and uPA secretion was enhanced by addition of FSH and FK to the organ culture media. (3) Segments of both rat and mouse seminiferous tubules at stages IX-XII in which the sperm residual bodies are absorbed into the Sertoli cells were also very sensitive to the addition of FSH to the organ culture. These results suggest that tPA in rat and mouse testes may play an essential role in the process of spermatogenesis and spermiation as well as in sperm residual body absorption.
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PMID:Hormonal regulation of plasminogen activator in rat and mouse seminiferous epithelium. 872 Jun 90