Actions of cyclosporin A preparation and Cremophor-EL in rabbit mesenteric artery and thoracic aorta in vitro

1992 ◽  
Vol 83 (2) ◽  
pp. 179-182 ◽  
Author(s):  
Ersin Yaris ◽  
Meral Tuncer ◽  
Mustafa Ilhan
Keyword(s):  
Cyclosporin A ◽  
Superior Mesenteric Artery ◽  
Thoracic Aorta ◽  
Mesenteric Artery ◽  
Cremophor El ◽  
Inhibitory Effects ◽  
Drug Induced ◽  
Slow Increase ◽  
Endothelium Dependent Relaxation

1. We studied the in vitro and direct effects of intravenous cyclosporin A preparation (Sandimmun) and its solvent (Cremophor-EL) on acetylcholine-induced endothelium-dependent relaxation, phenylephrine-induced contraction and drug-induced contraction of rabbit thoracic aorta and superior mesenteric artery segments. 2. At the lower concentration (5 μg/ml), cyclosporin A preparation inhibited endothelium-dependent relaxation of the superior mesenteric artery but not of the thoracic aorta. At this concentration cyclosporin A preparation augmented phenylephrine-induced contraction in both segments but by more in the superior mesenteric artery, and induced a slow increase in the tone of isolated superior mesenteric artery and thoracic aortic rings, which was greater in magnitude in the superior mesenteric artery than in the thoracic aorta. 3. Acetylcholine-induced endothelium-dependent relaxation was inhibited by cyclosporin A preparation (50 μg/ml) in both arteries but to a greater extent in the superior mesenteric artery. 4. The solvent of the intravenous cyclosporin A preparation (Cremophor-EL) in concentrations corresponding to those of the drug caused less inhibitory effects than cyclosporin A preparation on acetylcholine-induced endothelium-dependent relaxation, had comparable effects on phenylephrine-induced contraction, and produced similar contractions of both arteries. 5. The results indicate that Cremophor-EL may contribute to the inhibitory action of cyclosporin A preparation on acetylcholine-induced endothelium-dependent relaxation in the superior mesenteric artery, but is fully responsible for the smooth-muscle-contracting effect and the potentiation of phenylephrine-induced contraction in both arteries.

Identification of the immunophilins capable of mediating inhibition of signal transduction by cyclosporin A and FK506: roles of calcineurin binding and cellular location

1993 ◽  
Vol 13 (8) ◽  
pp. 4760-4769
Author(s):  
R J Bram ◽  
D T Hung ◽  
P K Martin ◽  
S L Schreiber ◽  
G R Crabtree
Keyword(s):  
Signal Transduction ◽  
T Cell ◽  
Cyclosporin A ◽  
Cell Function ◽  
Inhibitory Effects ◽  
Gene Deletions ◽  
Cyclophilin B ◽  
Intracellular Vesicles

The immunosuppressants cyclosporin A (CsA) and FK506 appear to block T-cell function by inhibiting the calcium-regulated phosphatase calcineurin. While multiple distinct intracellular receptors for these drugs (cyclophilins and FKBPs, collectively immunophilins) have been characterized, the functionally active ones have not been discerned. We found that overexpression of cyclophilin A or B or FKBP12 increased T-cell sensitivity to CsA or FK506, respectively, demonstrating that they are able to mediate the inhibitory effects of their respective immunosuppressants in vivo. In contrast, cyclophilin C, FKBP13, and FKBP25 had no effect. Direct comparison of the Ki of each drug-immunophilin complex for calcineurin in vitro revealed that although calcineurin binding was clearly necessary, it was not sufficient to explain the in vivo activity of the immunophilin. Subcellular localization was shown also to play a role, since gene deletions of cyclophilins B and C which changed their intracellular locations altered their activities significantly. Cyclophilin B has been shown previously to be located within calcium-containing intracellular vesicles; its ability to mediate CsA inhibition implies that certain components of the signal transduction machinery are also spatially restricted within the cell.

scholarly journals Obstruction of the Superior Mesenteric Artery Due to Emboli from the Thoracic Aorta in a Patient with Thromboangiitis Obliterans

2014 ◽  
Vol 7 (3) ◽  
pp. 320-324 ◽  
Author(s):  
Chiaki Kamiya ◽  
Juno Deguchi ◽  
Tadashi Kitaoka ◽  
Jun Suzuki ◽  
Keiko Abe ◽  
...  
Keyword(s):  
Superior Mesenteric Artery ◽  
Thoracic Aorta ◽  
Mesenteric Artery ◽  
Thromboangiitis Obliterans

Inhibitory Effects of Propofol on Acetylcholine-induced, Endothelium-dependent Relaxation and Prostacyclin Synthesis in Rabbit Mesenteric Resistance Arteries 

1999 ◽  
Vol 91 (4) ◽  
pp. 1080-1080 ◽  
Author(s):  
Akiko Yamashita ◽  
Junko Kajikuri ◽  
Masuo Ohashi ◽  
Yuichi Kanmura ◽  
Takeo Itoh
Keyword(s):  
Membrane Potential ◽  
Resistance Arteries ◽  
Inhibitory Effects ◽  
Membrane Hyperpolarization ◽  
Induced Membrane ◽  
Intact Rabbit ◽  
Prostacyclin Analog ◽  
Endothelium Dependent Relaxation ◽  
Prostacyclin Synthesis

Background Propofol (2,6-diisopropylphenol) modulates endothelium-dependent relaxation in some arterial preparations. The effect of propofol on endothelium-dependent, prostacyclin-mediated responses in mesenteric resistance arteries has not yet been clarified. Methods The effect of propofol was examined on acetylcholine-induced membrane potential changes in the presence of N(G)-nitro-L-arginine (L-NOARG) in endothelium-intact rabbit mesenteric resistance arteries in vitro. The effects of propofol were also examined on the endothelium-dependent relaxation and prostacyclin synthesis that was induced by acetylcholine in the presence of L-NOARG and nicardipine. The effect of propofol on the relaxation induced by a prostacyclin analogue was examined in strips treated with L-NOARG and diclofenac. Results Acetylcholine produced an initial and a slow membrane hyperpolarization. Propofol, 10 microM, and diclofenac each inhibited the acetylcholine-induced slow hyperpolarization, but not the initial hyperpolarization. Acetylcholine produced an endothelium-dependent relaxation that was significantly inhibited by propofol, 10 microM, and diclofenac. Propofol, 10 microM, greatly inhibited the acetylcholine-induced synthesis of prostacyclin, as did diclofenac. Propofol, 10 microM, had no effect on the relaxation induced by a prostacyclin analog. Conclusions In rabbit mesenteric resistance arteries, propofol inhibits the synthesis of prostacyclin and thus attenuates acetylcholine-induced, endothelium-dependent responses. Our results may help to explain why some actions seen with propofol in some preparations (e.g., vasoconstriction) are not seen after the endothelium is removed.

Detection of reticuloendothelial-depressing substance in shock

1965 ◽  
Vol 209 (1) ◽  
pp. 71-74 ◽  
Author(s):  
Benjamin Blattberg ◽  
Matthew N. Levy
Keyword(s):  
Escherichia Coli ◽  
Superior Mesenteric Artery ◽  
Whole Blood ◽  
Mesenteric Artery ◽  
The Other ◽  
In Vitro Method ◽  
Carbon Particles ◽  
Normal Rat

In an effort to find an in vitro method to detect the presence of reticuloendothelial-depressing substance (RDS), two tests were devised which measured phagocytic activity. One used carbon particles to measure phagocytosis and the other P32-labeled Escherichia coli. Neither method demonstrated an in vitro difference in granulopectic activity between dog plasmas from sham-operated and hemorrhagic-shock or superior mesenteric artery-occluded (SMAO) animals. An in vivo method was used in which the reticuloendothelial activity of the rat was measured in terms of the rate of clearance of injected carbon particles. Occlusion of the superior mesenteric artery of the rat led to the production of RDS. The RDS could be transferred to and demonstrated in a normal rat by means of SMAO rat whole blood, plasma, and dialysate of plasma, but not in RBC or plasma which had been dialyzed. Sham-operated animals were used as controls.

scholarly journals Expression of Green Fluorescent Protein as a Marker for Effects of Antileishmanial Compounds In Vitro

2001 ◽  
Vol 45 (12) ◽  
pp. 3654-3656 ◽  
Author(s):  
Sarah W. Kamau ◽  
Felix Grimm ◽  
Adrian B. Hehl
Keyword(s):  
Green Fluorescent Protein ◽  
Protein Expression ◽  
Real Time ◽  
Leishmania Infantum ◽  
Fluorescent Protein ◽  
Inhibitory Effects ◽  
Reliable Measure ◽  
Drug Induced ◽  
Green Fluorescent

ABSTRACT Transgenic Leishmania infantum promastigotes, which constitutively express green fluorescent protein (GFP) in their cytoplasm, were used to monitor the effects of antileishmanial compounds in real time. The GFP-based assay provided a reliable measure of drug-induced inhibitory effects on protein expression, resulting in a dynamic picture of the responses of leishmanial promastigotes to the compounds tested.

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