scholarly journals Polarized Entamoeba: A model for stable bleb driven motility

2019 ◽  
Author(s):  
Deepak Krishnan ◽  
Sudip Kumar Ghosh
Keyword(s):  
Adenosine Receptor ◽  
Leading Edge ◽  
Cell Aggregation ◽  
Protozoan Parasites ◽  
Membrane Flow ◽  
Adenosine Receptor Antagonist ◽  
Intermediate Phenotypes ◽  
Adenosine Receptor Agonist ◽  
Summary Statement ◽  
Entamoeba Invadens

AbstractProtozoan parasites Entamoeba histolytica and Entamoeba invadens formed a polarized phenotype, an elongated shape with a single leading edge and a trailing edge when treated with pentoxifylline. The leading edge of the polarized morphology was a spherical protrusion devoid of F-actin but with occasional F-actin scars, indicating the presence of bleb. The polarized form was stable bleb driven since the blebbing was limited to the leading edge. Pentoxifylline induced chemokinesis in Entamoeba as it switched the motility pattern from slow and random to fast and directionally persistent. Pentoxifylline speeded up the cell aggregation in E. invadens during growth and encystation due to enhanced chemotaxis of the polarized form. The transformation of non-polarized adherent trophozoites to nonadherent stable bleb driven form occurred via lamellipodial and bleb driven adherent intermediate phenotypes. The nonadherent polarized phenotype was highly motile under confinement and moved by rearward plasma membrane flow. In contrast to pentoxifylline, adenosine, the adenosine receptor agonist, stimulated the formation of multiple protrusions leading to random motility. Thus pentoxifylline might prevent lateral protrusions by inhibiting adenosine receptor, producing the monopodial polarized morphology.Summary statementPentoxifylline, the adenosine receptor antagonist induced a stable bleb driven polarized morphology in Entamoeba characterized by fast, directionally persistent and highly chemotactic motility.

Suppression of Generalized Seizures Activity by Intrathalamic 2-Chloroadenosine Application

2005 ◽  
Vol 230 (7) ◽  
pp. 501-505 ◽  
Author(s):  
Nurbay Ates ◽  
Gul Ilbay ◽  
Deniz Sahin
Keyword(s):  
Adenosine Receptor ◽  
Seizure Activity ◽  
Albino Rats ◽  
Seizure Duration ◽  
Seizure Severity ◽  
Adenosine Receptor Antagonist ◽  
Generalized Seizures ◽  
Adenosine Receptor Agonist ◽  
Severity Scores ◽  
Clonic Seizures

In the present study, we investigated the effects of micro-injecting 2-chloroadenosine (2-CADO; an adenosine receptor agonist) into the thalamus alone and with theophylline (a nonspecific adenosine receptor antagonist) pretreatment on pentylenetetrazol (PTZ)-induced tonic-clonic seizures in male Wistar albino rats. Following intrathalamic 2-CADO injection alone or theophylline pretreatment, 50 mg kg–1 PTZ was given ip after 1 and 24 hrs. The duration of epileptic seizure activity was recorded by cortical electroencephalogram (EEG), and seizure severity was behaviorally scored. Intrathalamic 2-CADO administration induced significant decreases in both seizure duration and seizure severity scores at 1 and 24 hrs, but the effects were more abundant on the seizures induced after 24 hrs. On the other hand, pretreatment with theophylline prevented the inhibitor effect of 2-CADO on seizure activity and increased both seizure duration and seizure scores. Present results suggest that the activation of adenosine receptors in the thalamus may represent another anticonvulsant/modulatory site of adenosine action during the course of the PTZ-induced generalized tonic-clonic seizures and provide additional data for the involvement of the adenosinergic system in the generalized seizures model.

Interactions between alpha-adrenoceptors and adenosine receptors on microvascular smooth muscle

1991 ◽  
Vol 260 (5) ◽  
pp. H1655-H1666 ◽  
Author(s):  
K. Nishigaki ◽  
J. E. Faber ◽  
M. Ohyanagi
Keyword(s):  
Adenosine Receptor ◽  
Adenosine Receptors ◽  
Inhibitory Effect ◽  
Inhibitory Effects ◽  
Receptor Stimulation ◽  
Alpha Adrenoceptors ◽  
Adenosine Receptor Antagonist ◽  
Adenosine Receptor Agonist ◽  
Muscle Concentration ◽  
Tissue Acidosis

alpha 2-Adrenoceptor but not alpha 1-adrenoceptor constriction of arterioles is selectively inhibited by tissue acidosis, ischemia, and increased metabolic rate. To further examine neural-local interactions, we studied the effect of adenosine receptor stimulation on alpha 1- or alpha 2-adrenoceptor constriction. Intravital microscopy was used to study large arterioles (133 +/- 3 microns diam; mean +/- SE), small arterioles (16 +/- 1 microns), and large venules (178 +/- 3 microns) of rat cremaster skeletal muscle. Concentration-response (diameter change) curves were obtained for bath-added norepinephrine in the presence of either rauwolscine or prazosin to provide selective alpha 1- and alpha 2-constriction, respectively. The adenosine receptor agonist 5'-N-ethylcarboxamidoadenosine (2.24 x 10(-8) M) significantly attenuated both alpha 1- and alpha 2-constriction by 5- to 20-fold; alpha 1-constriction was three- to fourfold more sensitive than alpha 2-constriction. Similar inhibitory effects were obtained with adenosine (2.24 x 10(-6) M). The adenosine receptor antagonist 8-[4-[N(2-aminoethyl)carbamoylmethoxy]phenyl]-1,3-dipropylxanthine (0.7 microM) reversed the inhibitory effect of adenosine, which implicates extracellular A2 adenosine receptors. Intrinsic tone in large vessels was unaffected by adenosine receptor stimulation but was completely inhibited in small arterioles. These findings suggest that both alpha 2- and especially alpha 1-adrenoceptor constriction and intrinsic tone (of small but not large arterioles) are inhibited by physiologically relevant concentrations of adenosine.

Adenosine stimulates glycolytic flux in isolated perfused rat hearts by A1-adenosine receptors

1989 ◽  
Vol 257 (6) ◽  
pp. H1952-H1957 ◽  
Author(s):  
D. A. Wyatt ◽  
M. C. Edmunds ◽  
R. Rubio ◽  
R. M. Berne ◽  
R. D. Lasley ◽  
...  
Keyword(s):  
Adenosine Receptor ◽  
Adenosine Receptors ◽  
Receptor Agonist ◽  
Glycolytic Flux ◽  
Adenosine Receptor Antagonist ◽  
Exogenous Glucose ◽  
Rat Hearts ◽  
Adenosine Receptor Agonist ◽  
Perfused Rat Hearts ◽  
A1 Adenosine Receptors

This study was designed to assess the role of adenosine in the regulation of exogenous glucose utilization by myocardium. Perfusion of isolated rat hearts with buffer containing D-[3-3H]glucose and analysis of the coronary effluent for 3H2O production was used as an indicator of glycolytic flux. Initially, glycolytic flux was determined during five different conditions: 1) normoxia; 2) normoxia plus 100 microM adenosine; 3) normoxia plus 100 microM adenosine and 10 microM 8-(sulfophenyl)-theophylline (SPT), an adenosine receptor antagonist; 4) hypoxia; and 5) hypoxia plus 10 microM SPT. Both adenosine and hypoxia produced an approximate threefold increase in glycolytic flux that was attenuated by adenosine receptor blockade with SPT. Next, hearts were perfused during normoxic conditions with various concentrations of either R-phenylisopropyladenosine (PIA), an A1-adenosine receptor agonist, or 5'-N-ethylcarboxamidoadenosine (NECA), an A2-adenosine receptor agonist. Significant increases in glycolytic flux occurred with PIA, whereas NECA treatment resulted in only a marginal stimulation of glycolytic flux. These data provide evidence that: 1) exogenous adenosine stimulated glycolytic flux in the normoxic myocardium; 2) endogenous adenosine stimulated glycolytic flux during hypoxia; and 3) the effect of adenosine on glycolytic flux was mediated by interaction with A1-adenosine receptors.

scholarly journals Morphological and Motility Features of the Stable Bleb-Driven Monopodial Form of Entamoeba and Its Importance in Encystation

2020 ◽  
Vol 88 (8) ◽  
Author(s):  
Deepak Krishnan ◽  
Sudip Kumar Ghosh
Keyword(s):  
Sol Gel ◽  
Leading Edge ◽  
Cell Aggregation ◽  
Time Lapse ◽  
Purine Nucleotides ◽  
Content Type ◽  
Adenosine Antagonist ◽  
Entamoeba Invadens ◽  
Directional Cell Migration

ABSTRACT Entamoeba histolytica and its reptilian counterpart and encystation model Entamoeba invadens formed a polarized monopodial morphology when treated with pentoxifylline. This morphology was propelled by retrograde flow of the cell surface resulting from a cyclic sol-gel conversion of cytoplasm and a stable bleb at the leading edge. Pentoxifylline treatment switched the unpolarized, adherent trophozoites to the nonadherent, stable bleb-driven form and altered the motility pattern from slow and random to fast, directionally persistent, and highly chemotactic. Interestingly, exogenously added adenosine produced multiple protrusions and random motility, an opposite phenotype to that of pentoxifylline. Thus, pentoxifylline, an adenosine antagonist, may be inducing the monopodial morphology by preventing lateral protrusions and restricting the leading edge to one site. The polarized form of E. invadens was aggregation competent, and time-lapse microscopy of encystation revealed its appearance during early hours, mediating the cell aggregation by directional cell migration. The addition of purine nucleotides to in vitro encystation culture prevented the formation of polarized morphology and inhibited the cell aggregation and, thus, the encystation, which further showed the importance of the polarized form in the Entamoeba life cycle. Cell polarity and motility are essential in the pathogenesis of Entamoeba parasites, and the stable bleb-driven polarized morphology of Entamoeba may also be important in invasive amoebiasis.

scholarly journals Mechanosensitivity of mouse tracheal ciliary beat frequency: roles for Ca2+, purinergic signaling, tonicity, and viscosity

2007 ◽  
Vol 292 (3) ◽  
pp. L614-L624 ◽  
Author(s):  
Scot L. Winters ◽  
C. William Davis ◽  
Richard C. Boucher
Keyword(s):  
Adenosine Receptor ◽  
Purinergic Signaling ◽  
Beat Frequency ◽  
Ciliary Beat Frequency ◽  
Adenosine Receptor Antagonist ◽  
Viscosity Increase ◽  
Adenosine Receptor Agonist ◽  
Microscopy Image ◽  
Osmotic Agent ◽  
Ciliary Beat

Mechanosensitivity is hypothesized to participate in the regulation of ciliary beat frequency (CBF) in airway epithelia. To investigate this hypothesis, CBF in excised mouse trachea was monitored (microscopy image analysis) while varying mucosal shear (perfusate velocity and/or viscosity; planar flow). CBF increased within minutes of step increase to steady shear stress as small as 10−3 Pa and decreased within minutes of shear reduction (≤10−4 Pa). CBF response was directional, being less with cephalad vs. caudal flow, and was reduced in trachea from mutant mice lacking P2Y2 receptors, as well as by administration of the Ca2+ chelator EGTA, the Ca2+ channel inhibitor La3+, the nucleotide phosphohydrolase apyrase, the metabolically stabilized adenosine receptor agonist 5′-( N-ethylcarboxamido)adenosine, the osmotic agent mannitol, and the viscosity modifier dextran. Brief exposure to exogenous ATP, a candidate mediator, augmented CBF response, although augmentation declined with higher ATP concentration (5.0 vs. 0.1 mM) or longer ATP exposure before shear (55 vs. 20 min). Prolonged extended exposure (45 min) to the metabolically stabilized ATP analog ATPγS [adenosine 5′-(3-thiotriphosphate), 0.1 mM] inhibited CBF response to shear. Furthermore, neither ATP nor ATPγS substantially increased CBF in the relative absence of shear. With viscosity increase or shear withdrawal apyrase evoked CBF stimulation, inhibitable by the adenosine receptor antagonist 8-( p-sulfophenyl)theophylline. Thus CBF response to shear is finely tuned, directional, La3+ sensitive, likely dependent on extracellular Ca2+ and ATP, involving P2Y2 and adenosine receptor activations, influenced by shear history, tonicity, viscosity, and metabolism/exposure of ATP, and thus reflective of a complex interplay of physical and biochemical actions.

Renal effects of endotoxin in the male rat

1987 ◽  
Vol 253 (2) ◽  
pp. F244-F250 ◽  
Author(s):  
P. C. Churchill ◽  
A. K. Bidani ◽  
M. M. Schwartz
Keyword(s):  
Adenosine Receptor ◽  
Significant Contribution ◽  
Male Rat ◽  
Tubular Injury ◽  
Fibrin Deposition ◽  
Renal Effects ◽  
Adenosine Receptor Antagonist ◽  
Acid Clearance ◽  
Adenosine Receptor Agonist ◽  
Phenylisopropyl Adenosine

A new model of acute reduction in renal function induced by a 2-h infusion of endotoxin (Escherichia coli 026:B6 lipopolysaccharide, 5 mg X kg-1 X h-1) was developed in the anesthetized male rat. In the absence of significant glomerular fibrin deposition, inulin clearance (glomerular filtration rate, GFR) was reduced from 8.50 +/- 0.34 to 4.01 +/- 0.45 ml X kg-1 X min-1 (P less than 0.0005), and p-aminohippuric acid clearance was reduced from 23.7 +/- 0.8 to 15.0 +/- 1.8 ml X kg-1 X min-1 (P less than 0.0005), indicating a hemodynamic basis for the reduction in GFR. The lack of morphological tubular injury and a decreased fractional Na excretion (from 2.63 +/- 0.27 to 0.54 +/- 0.09%, P less than 0.00005) exclude a significant contribution of tubular mechanisms to the reduction in GFR. Administration of theophylline, a competitive adenosine receptor antagonist, concurrently with or immediately after the endotoxin infusion, restored inulin and PAH clearances and fractional Na excretion toward normal. Moreover, the renal effects of endotoxin were mimicked by intravenous administration of N6-(L-phenylisopropyl)-adenosine (L-PIA), an adenosine receptor agonist, and the effects of L-PIA in turn were also antagonized by theophylline. These data suggest that adenosine plays a significant role in mediating the hemodynamic derangements of this model.

Effect of adenosine uptake inhibition on the nature and potency of theophylline as a presynaptic adenosine receptor antagonist

1980 ◽  
Vol 58 (7) ◽  
pp. 805-809 ◽  
Author(s):  
A. S. Clanachan ◽  
M. J. Muller
Keyword(s):  
Receptor Antagonist ◽  
Adenosine Receptor ◽  
Vas Deferens ◽  
Rat Vas Deferens ◽  
Uptake System ◽  
Uptake Inhibition ◽  
Adenosine Receptor Antagonist ◽  
Adenosine Uptake ◽  
Adenosine Receptor Agonist ◽  
Adenosine Analogue

The nature and potency of theophylline as a presynaptic adenosine receptor antagonist was investigated in rat vas deferens in vitro.Schild plots were constructed and the pA2 and the slope were determined when the presynaptic adenosine receptor agonist was (a) adenosine alone, (b) adenosine following adenosine uptake inhibition by hydroxynitrobenzylthioguanosine, and (c) 2-chloroadenosine, a potent adenosine analogue which appears not to be a substrate for the adenosine uptake system. The pA2 values for theophylline were 3.80, 4.58, and 5.61, respectively, and the slopes of the Schild plots were 0.58, 0.71, and 0.78, respectively.The variation in the apparent potency of theophylline as a presynaptic adenosine receptor antagonist is explained according to Furchgott's prediction that removal of an agonist from the vicinity of its receptor upsets the equilibrium between agonist and receptor and so may influence antagonist – receptor interactions.Because adenosine uptake varies among tissues, this process should be eliminated before attempting to compare potencies of adenosine receptor antagonists or to classify adenosine receptors by pA2 values.

CPX, a selective A1-adenosine-receptor antagonist, regulates intracellular pH in cystic fibrosis cells

1995 ◽  
Vol 269 (1) ◽  
pp. C226-C233 ◽  
Author(s):  
V. Casavola ◽  
R. J. Turner ◽  
C. Guay-Broder ◽  
K. A. Jacobson ◽  
O. Eidelman ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Receptor Antagonist ◽  
Intracellular Ph ◽  
Adenosine Receptor ◽  
Ph Regulation ◽  
Cystic Fibrosis Transmembrane Regulator ◽  
Wild Type ◽  
A1 Adenosine Receptor ◽  
Adenosine Receptor Antagonist ◽  
Cystic Fibrosis Transmembrane

The selective A1-adenosine-receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (CPX), has been reported to activate Cl- efflux from cystic fibrosis cells, such as pancreatic CFPAC-1 and lung IB3 cells bearing the cystic fibrosis transmembrane regulator(delta F508) mutation, but has little effect on the same process in cells repaired by transfection with wild-type cystic fibrosis transmembrane regulator (O. Eidelman, C. Guay-Broder, P. J. M. van Galen, K. A. Jacobson, C. Fox, R. J. Turner, Z. I. Cabantchik, and H. B. Pollard. Proc. Natl. Acad. Sci. USA 89: 5562-5566, 1992). We report here that CPX downregulates Na+/H+ exchange activity in CFPAC-1 cells but has a much smaller effect on cells repaired with the wild-type gene. CPX also mildly decreases resting intracellular pH. In CFPAC-1 cells, this downregulation is dependent on the presence of adenosine, since pretreatment of the cells with adenosine deaminase blocks the CPX effect. We also show that, by contrast, CPX action on these cells does not lead to alterations in intracellular free Ca2+ concentration. We conclude that CPX affects pH regulation in CFPAC-1 cells, probably by antagonizing the tonic action of endogenous adenosine.

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