Endotoxin Inhibits Prostacyclin Release From Rabbit Aorta

1981 ◽  
Author(s):  
J Zahavi ◽  
A C Honey ◽  
J Westwick ◽  
V V Kakkar
Keyword(s):  
Platelet Aggregation ◽  
Rabbit Aorta ◽  
Inhibitory Effect ◽  
White Female ◽  
Time Intervals ◽  
E Coli ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
The Mean ◽  
Dose Dependent

Released prostacyclin (PGI2) activity has been studied in aortic rings of 19 New Zealand white female rabbits. These rings produced a potent inhibitor of platelet aggregation, identified as PGI2. All the rabbits were anaesthetized with pentobarbital and thereafter a solution of endotoxin (E. Coli, 0111, B4, Difco Lab.) was injected intravenously to 7 rabbits (304μg/kg every 15 min during 1 hour to achieve an estimated plasma level of 1-2 μg/ml). Another 5 rabbits served as controls and were injected with saline. After 1 hour the aorta was rapidly excised, cleaned, cut into small rings and the released PGI2 activity studied at various time intervals (5-30 min) at 37°C. The mean release of PGI2 (in pg/mg wet tissue) in the control rabbits was 201 (range 50-443). It decreased significantly to 104 (range 0-237) after 30 min. In the endotoxaemic rabbits, the initial PGI2 release was only 73 (range 0-329) (p<0,008 compared to control rabbits). This level did not change with time and was 71.9 (range 0-261) after 30 min suggesting that the “endotoxinemic” vessels were initially relatively exhausted and were not able to release PGI2. In the remaining 7 rabbits the aorta was removed immediately after anaesthesia and aortic rings incubated for 5-30 min Krebs-Henleit buffer or endotoxin 0.2-10 μg/ml and the released PGI2 activity studied. There was a dose dependent inhibition which was more pronounced after 30 min incubation.The decrease in PGI2 release from rabbit aorta following endotoxaemia removes the inhibitory effect on platelet aggregation of the arterial vessel wall and consequently may contribute to the development of a thrombogenic state.

Mepacrine Blockade of Arachidonate-lnduced Washed Platelet Aggregation: Relationship to Mepacrine Inhibition of Platelet Cyclooxygenase

1983 ◽  
Vol 50 (04) ◽  
pp. 784-786 ◽  
Author(s):  
Amiram Raz
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Thromboxane A2 ◽  
Inhibitory Effect ◽  
Thromboxane B2 ◽  
Concomitant Increase ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Arachidonate Release ◽  
Dose Dependent

SummaryMepacrine, in addition to its established antilipolytic activity, was also found to inhibit the conversion of 14C-arachidonic acid to 14C-thromboxane B2 in human washed platelets. In the concentration range of 3.33-33 μM, mepacrine exerted a dose dependent inhibition of arachidonate conversion to thromboxane B2 in parallel to inhibition of arachidonate-induced platelet aggregation. Mepacrine inhibition of thromboxane formation was not accompanied by a concomitant increase in other cyclooxygenase products. Furthermore, mepacrine did not affect platelet transformation of added prostaglandin H2 to thromboxane A2 and other products. These results indicate that mepacrine inhibits the cyclooxygenase enzyme and not thromboxane synthase. In washed platelets, mepacrine inhibition of arachidonic acid conversion to thromboxane A2 appears to be a major factor in the overall inhibitory effect of the compound on the combined process of arachidonate release from cellular phospholipids and its conversion to proaggregatory products.

Nickel inhibits endothelin-induced contractions of vascular smooth muscle

1990 ◽  
Vol 258 (6) ◽  
pp. C1025-C1030 ◽  
Author(s):  
K. Blackburn ◽  
R. F. Highsmith
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Isometric Force ◽  
Inhibitory Effect ◽  
Rat Aorta ◽  
Porcine Coronary Artery ◽  
Force Development ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Dose Dependent

Endothelin (ET)-induced contractions of vascular smooth muscle (VSM) are dependent on extracellular Ca2+ yet display only partial sensitivity to L-type Ca2+ antagonists. The purpose of this study was to evaluate the effect of nickel (Ni2+), a Ca2+ channel antagonist with clearly documented differential potency toward L- vs. T-type Ca2+ currents on ET-mediated contractions in VSM. Treatment of rings of left anterior descending porcine coronary artery (LAD) with Ni2+ produced a profound dose-dependent inhibition of isometric force development in response to porcine ET (ET-1). At a concentration of 360 microM, Ni2+ exerted a significant inhibitory effect on contracture in response to doses of ET-1 ranging from 3 to 100 nM. In contrast, the same concentration of Ni2+ failed to significantly affect peak force development in response to KCl depolarization (5-77 mM) or to phenylephrine (0.3-30 mM). In addition, 360 microM Ni2+ significantly inhibited the contractile response of rat aorta to 10 nM ET-1. We conclude that ET-1 activates a Ni2(+)-sensitive process in VSM which may signal an additional Ca2+ influx pathway that appears to be functionally distinct from the L-type Ca2+ channel.

Sodium cromoglycate: evidence of tachykinin antagonist activity in the human skin

1993 ◽  
Vol 75 (1) ◽  
pp. 167-172 ◽  
Author(s):  
D. C. Crossman ◽  
M. R. Dashwood ◽  
G. W. Taylor ◽  
R. Wellings ◽  
R. W. Fuller
Keyword(s):  
Sodium Cromoglycate ◽  
Human Skin ◽  
High Performance ◽  
Gel Filtration ◽  
Inhibitory Effect ◽  
Intradermal Injection ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Dose Dependent

The mechanism of action of the antiasthmatic drug sodium cromoglycate (SCG) is unclear. One possibility is that SCG antagonizes the effects of the tachykinin substance P (SP), an agent known to cause airway edema. However, when SP is inhaled by humans, it has no demonstrable effect on airway function; therefore, the possibility that SCG prevents SP-induced changes in microvascular permeability was examined in human skin in vivo where potent edema-producing effects are seen. SCG (5–500 nmol) caused significant (P < 0.05) dose-dependent inhibition of SP-induced edema (wheal) formation when coadministered by intradermal injection. There was no effect on the nonreceptor-mediated flare response. SCG also significantly (P < 0.05) inhibited the wheal response to the related tachykinin neurokinin B but had no inhibitory effect on the cutaneous responses to histamine and prostaglandin E2. In addition, SCG (0.1–10 mM) caused dose-dependent inhibition of binding of SP labeled with 125I-labeled Bolton-Hunter to a number of tissues known to contain SP binding sites, as assessed by autoradiography. These concentrations were equivalent to the final concentrations of SCG found to inhibit the wheal response in the skin. The possibility that SCG interacted with SP was investigated both by gel filtration and high-performance liquid chromatography. No strong interaction was demonstrated with an 8,000 M excess of SCG under both hydrophobic and hydrophilic conditions. These results raise the possibility that SCG may have tachykinin antagonist properties.

scholarly journals Somatostatinergic ligands in dopamine-sensitive and -resistant prolactinomas

2008 ◽  
Vol 158 (5) ◽  
pp. 595-603 ◽  
Author(s):  
Alessandra Fusco ◽  
Ginette Gunz ◽  
Philippe Jaquet ◽  
Henry Dufour ◽  
Anne Laure Germanetti ◽  
...  
Keyword(s):  
Thymidine Incorporation ◽  
Primary Cultures ◽  
Receptor Subtypes ◽  
Mrna Levels ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
The Mean ◽  
Design And Methods ◽  
Dose Dependent ◽  
Receptor Mrnas

ObjectiveTen percent of patients with prolactinoma fail to respond with normalization of prolactin (PRL) and tumor shrinkage under dopamine agonist (DA) therapy. The resistance to treatment is linked to a loss of dopamine receptor 2 (D2DR). Prolactinomas express somatostatin (SST) receptor subtypes, SSTR1, 2, and 5. The aim of this study was to determine whether different SST compounds could overcome the resistance to DA in prolactinomas.Design and methodsThe efficacy of SSTR1, SSTR2, and SSTR5 ligands; the universal SST ligand, SOM230; and the chimeric SST-DA compound, BIM-23A760, was compared with cabergoline in suppressing PRL secretion from primary cultures of ten prolactinomas (six DA responders and four DA resistant). Receptor mRNAs were assessed by quantitative PCR.ResultsThe mean mRNA levels for D2DR, SSTR1, SSTR2, and SSTR5 were 92.3±47.3, 2.2±1.4, 1.1±0.7, and 1.6±0.6 copy/copy β-glucuronidase (β-Gus) respectively. The SSTR1 agonist, BIM-23926, did not suppress PRL in prolactinomas. In a DA-resistant prolactinoma, it did not inhibit [3H]thymidine incorporation. The SSTR5 compound, BIM-23206, produced a dose-dependent inhibition of PRL release similar to that of cabergoline in three DA-sensitive prolactinomas. BIM-23A760 produced a maximal PRL inhibition superimposable to that obtained with cabergoline with a lower EC50 (0.5±0.1 vs 2.5±1.5 pmol/l). In DA-resistant prolactinomas, BIM-23206 and SOM230 were ineffective. Cabergoline and BIM-23A760 produced a partial inhibition of PRL secretion (19±6 and 21±3% respectively).ConclusionAlthough the SSTRs are expressed in prolactinomas, the somatostatinergic ligands analyzed do not appear to be highly effective in suppressing PRL. D2DR remains the primary target for effective treatment of prolactinomas.

Antiplatelet Effect of Hsien-Ho-T'sao (Agrimonia Pilosa)

1985 ◽  
Vol 13 (01n04) ◽  
pp. 109-118 ◽  
Author(s):  
Jih-Pyang Wang ◽  
Mei-Feng Hsu ◽  
Che-Ming Teng
Keyword(s):  
Platelet Rich Plasma ◽  
Atp Release ◽  
Water Extract ◽  
Creatine Phosphate ◽  
Inhibitory Effect ◽  
Malondialdehyde Formation ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Induced Aggregation ◽  
Dose Dependent

The water extract of Hsien-Ho-T'sao (HHT) produced a dose-dependent inhibition on collagen-induced aggregation of platelet-rich plasma (PRP). The IC50 was about 3.5 mg/ml. In addition, HHT inhibited also the aggregation induced by ADP, A23187 or arachidonate in PRP. Greater inhibition was observed in the preparation of washed platelets. Increase of the calcium concentration in medium could not overcome the inhibitory effect of HHT. ATP release from platelets induced by collagen or A23187 was inhibited by HHT. In the presence of EDTA, ATP release caused by thrombin or A23187 was also inhibited by HHT. Malondialdehyde and thromboxane B2 formation was greatly inhibited by HHT in platelets challenged by collagen and thrombin. In arachidonate-stimulated platelets, thromboxane B2, but not malondialdehyde formation was inhibited. HHT showed more marked inhibition on aggregation in the presence of indomethacin, creatine phosphate/creatine phosphokinase or a combination of both. Hydrogen peroxide-induced hemolysis was makred reduced by HHT. It was concluded that HHT might have some membrane-active properties which interfered with the activation of phospholipase A2.

scholarly journals A Strain of Enterococcus faecium (18C23) Inhibits Adhesion of Enterotoxigenic Escherichia coli K88 to Porcine Small Intestine Mucus

2000 ◽  
Vol 66 (10) ◽  
pp. 4200-4204 ◽  
Author(s):  
L. Z. Jin ◽  
R. R. Marquardt ◽  
X. Zhao
Keyword(s):  
Escherichia Coli ◽  
Small Intestine ◽  
Enterococcus Faecium ◽  
Culture Supernatant ◽  
Ph Effect ◽  
Enterotoxigenic Escherichia Coli ◽  
E Coli ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Dose Dependent

ABSTRACT Few studies, if any, have addressed the adhesion of enterococci to the intestinal mucosa and their interference with the adhesion of pathogens, although more than 60% of probiotic preparations in the market contain strains of enterococci. The objective of this study was to investigate if Enterococcus faecium 18C23 has the ability to inhibit the adhesion of Escherichia coli K88ac and K88MB to the small intestine mucus of piglets. Approximately 9% ofE. faecium 18C23 organisms adhered to the small intestine mucus, and the adhesion was found to be specific. Living E. faecium 18C23 culture efficiently inhibited the adhesion ofE. coli K88ac and K88MB to the piglet intestine mucus. Inhibition of the adhesion of E. coli K88ac to the small intestine mucus was found to be dose dependent. Inhibition of >90% was observed when 109 CFU or more of living E. faecium 18C23 culture per ml was added simultaneously withE. coli to immobilized mucus. The substances from both the 18C23 cells and the spent culture supernatant contributed to the inhibition of adhesion of E. coli K88 to the small intestine mucus receptors. The inhibiting effect was not solely a pH effect since considerable inhibitory action was demonstrated after neutralizing the mixture or spent culture supernatant to pH 7.0. Part of the inhibition of adhesion of E. coli K88ac by E. faecium 18C23 or its supernatant might occur through steric hindrance.

Effects of Methylprednisolone and Hydrocortisone on Aggregation of Rabbit Platelets Induced by Arachidonic Acid and Other Aggregating Substances

1981 ◽  
Vol 46 (04) ◽  
pp. 676-679 ◽  
Author(s):  
Frank Glass ◽  
Howard Lippton ◽  
Philip J Kadowitz
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
Adenosine Diphosphate ◽  
Actual Mechanism ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
The Difference ◽  
Induced Aggregation ◽  
Dose Dependent

SummaryThe effects of methylprednisolone and hydrocortisone on platelet aggregation induced by arachidonic acid (AA), collagen, adenosine diphosphate (ADP), prostaglandin (PG) H2, and a stable PGH2 analog, were studied in platelet-rich plasma (PRP) from the rabbit. Incubation of either steroid in PRP inhibited AA-, collagen- and ADP-induced platelet aggregation in a concentration-related manner. The dose of methylprednisolone required to inhibit 0.02 mM AA-induced aggregation was lower than that required to inhibit either 0.08 μg/ml collagen or 0.2 μM ADP-induced aggregation. Methylprednisolone produced a dose dependent inhibition of platelet aggregation induced by PGH2 and the stable PGH2 analog. In washed platelets methylprednisolone was more effective in inhibiting AA-induced aggregation than ADP- or collagen-induced aggregation; however, the difference in effect was less than in PRP. Platelet responses to AA in PRP from rabbits treated with hydrocortisone or methylprednisolone, 100 mg/kg i.v., were inhibited in a transient manner, whereas aggregation induced by ADP under similar conditions was unchanged. Since inhibition of aggregation elicited by AA occurred at concentrations which do not influence PGH2-, PGH2 analog-, collagen- or ADP-induced aggregation, the present data suggest that the steroids may inhibit the incorporation, the release, or the metabolism of arachidonic acid in platelets. The actual mechanism of this relatively specific inhibition of AA-induced aggregation by anti-inflammatory steroids is uncertain but may be related to the membrane “stabilizing” properties of methylprednisolone and hydrocortisone.

Synthetic atrial peptide inhibits intracellular calcium release in smooth muscle

1986 ◽  
Vol 250 (1) ◽  
pp. C171-C174 ◽  
Author(s):  
K. D. Meisheri ◽  
C. J. Taylor ◽  
H. Saneii
Keyword(s):  
Smooth Muscle ◽  
Calcium Release ◽  
Rabbit Aorta ◽  
Inhibitory Effect ◽  
Physiological Salt Solution ◽  
Phasic Contraction ◽  
Dependent Inhibition ◽  
Isolated Rabbit Aorta ◽  
Dose Dependent Inhibition ◽  
45Ca Efflux

The effects of a synthetic atrial peptide (atriopeptin II; AP II) on the agonist-induced intracellular Ca2+ release was examined in the isolated rabbit aorta. The agonist-induced phasic contraction in a Ca2+-free physiological salt solution containing 2 mM ethyleneglycol-bis(beta-aminoethyl-ether)-N,N'-tetraacetic acid (EGTA-PSS) was used as an indicator of the intracellular Ca2+ release. The addition of AP II (10(-9)-10(-7) M) for 15 min to the tissue during the EGTA-PSS exposure caused a dose-dependent inhibition of norepinephrine (NE; 10(-6) M)-induced phasic contraction. The half-maximal inhibiting concentration of AP II was 3 X 10(-9) M, with 10(-7) M AP II causing 91% inhibition. This was confirmed by studying the inhibitory effect of AP II (10(-7) M) on NE-stimulated 45Ca efflux. Furthermore, the internal Ca2+ release by histamine (10(-5) M) and caffeine (25 mM), both of which share this internal Ca2+ pool with NE, was also inhibited by AP II. Thus AP II appears to be a potent inhibitor of the intracellular Ca2+ release that is utilized by various agonists for the activation of vascular smooth muscle. This may be an important mechanism by which AP II produces relaxation of blood vessels.

Inhibition of sarcolemmal Na+-K+-ATPase by palmitoyl carnitine: potentiation by propranolol

1985 ◽  
Vol 248 (1) ◽  
pp. H75-H81
Author(s):  
J. H. Kramer ◽  
W. B. Weglicki
Keyword(s):  
Bovine Serum Albumin ◽  
Atpase Activity ◽  
Cardiac Myocytes ◽  
Inhibitory Effect ◽  
Inhibition Activity ◽  
Irreversible Inhibition ◽  
Palmitoyl Carnitine ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Dose Dependent

Native sarcolemma (SL) from adult canine cardiac myocytes (Na+-K+-ATPase activity 74.2 +/- 3.0 mumol X mg-1 X h-1) was preincubated (10 min, 37 degrees C, pH 7.2) with 1) 20-600 microM palmitoyl carnitine, 2) 250 nM-2.5 mM propranolol, or 3) 20-600 microM palmitoyl carnitine plus propranolol at various concentrations (0.0, 0.025, 0.25, 0.5, 1.0, and 2.5 mM); after preincubation, Na+-K+-ATPase activity was assayed. Palmitoyl carnitine alone (series 1) had no effect on ATPase activity over the range of 20-400 microM but was inhibitory (30%) at 600 microM. Propranolol alone (series 2) did not alter ATPase activity at any concentration. When SL membranes were exposed to both palmitoyl carnitine and propranolol (series 3), a dose-dependent inhibition of ATPase activity was observed. The inhibitory effect was not reversed by 3.0% bovine serum albumin. Propranolol concentrations greater than 0.025 mM significantly inhibited the activity of SL exposed to palmitoyl carnitine (above 150 microM). Palmitoyl carnitine and propranolol do not have to be added simultaneously to produce combined inhibition. Activity was inhibited 50% when SL were pretreated with 100 microM palmitoyl carnitine followed by addition of 2.5 mM propranolol no inhibition occurred if preincubation conditions were reversed. Thus exposure of SL to propranolol and reported physiological levels of palmitoyl carnitine leads to irreversible inhibition of the Na+-K+-ATPase, which may be due to the combined membrane-perturbant actions of these amphipathic agents.

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