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.

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.

Mechanism of activation of isolated rabbit aorta by PGH2 analogue U-44069

1981 ◽  
Vol 241 (5) ◽  
pp. C243-C249 ◽  
Author(s):  
R. Loutzenhiser ◽  
C. van Breemen
Keyword(s):  
Smooth Muscle ◽  
Contractile Response ◽  
Rabbit Aorta ◽  
Calcium Content ◽  
Prior Exposure ◽  
Maximal Tension ◽  
Isolated Rabbit Aorta ◽  
Free Media ◽  
45Ca Efflux ◽  
Stimulation Of

The effects of a stable analogue of PGH2 on 45Ca fluxes and tension were studied in the isolated rabbit aorta. U-44069 produced maximal tension responses at a concentration of 10(-7) M. The analogue increased smooth muscle Ca2+ content and increased the unidirectional 45Ca influx. U-44069 also induced contractions of reduced magnitude in the absence of external Ca2+ and caused a transient stimulation of 45Ca efflux, suggesting that the analogue releases intracellularly bound Ca2+. Both the contractile response in CA2+-free media and the stimulation of 45Ca efflux were greatly attenuated by prior exposure to norepinephrine. The analogue-induced contractions in Ca2+-free media were also prevented by prior exposure to histamine but not angiotensin II. D-600 completely blocked the U-44069-induced gain in calcium content (IC50 = 10(-6) M) but inhibited the contractile response by only 40%. It was concluded that the PGH2 analogue activates rabbit aorta by activating a CA2+ influx pathway and releasing a fraction of the intracellular Ca2+ pool that is sensitive to norepinephrine and other agonists.

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.

Medial Smooth Muscle Cell Proliferation in the Balloon Injured Rabbit Aorta: Effect of a Thiazole Compound with Platelet Inhibitory Activity

1984 ◽  
Vol 51 (01) ◽  
pp. 075-078 ◽  
Author(s):  
R G Schaub ◽  
C A Simmons
Keyword(s):  
Smooth Muscle ◽  
Platelet Aggregation ◽  
Balloon Catheter ◽  
Rabbit Aorta ◽  
Surface Characteristics ◽  
Inhibitory Effect ◽  
Lesion Size ◽  
Blue Staining ◽  
Morphologic Characteristics ◽  
Time Period

SummaryTwenty-seven adult male New Zealand rabbits (3–4 kgs) were used in this study. Six rabbits received vehicle, 3 groups of 6 each received doses of 4,5-bis(p-methoxyphenyl)-2-(trifluoromethyl)- thiazole, (U-53,059), at 0.3 mg/kg, 3.0 mg/kg and 30.0 mg/kg/day respectively. Drug and vehicle doses were given orally each day starting 3 days before balloon injury and continuing for the entire 2 week time period. Three rabbits were used as nontreated sham controls. In the vehicle and U-53,059 treated groups aortae were denuded of endothelial cells by balloon catheter injury. Two weeks after injury platelet aggregation to collagen was measured and the aortae removed for analysis of surface characteristics by scanning electron microscopy and lesion size by morphometry. All doses of U-53,059 inhibited platelet aggregation. The 3.0 and 30.0 mg/kg groups had the greatest inhibitory effect. All balloon injured aortae had the same morphologic characteristics. All vessels had similar extent and intensity of Evan’s blue staining, similar areas of leukocyte/platelet adhesion, and a myointimal cell cover of transformed smooth muscle cells. The myointimal proliferative response was not inhibited at any of the drug doses studied.

scholarly journals Characterization of the inositol 1,4,5-trisphosphate-induced calcium release from permeabilized endocrine cells and its inhibition by decavanadate and p-hydroxymercuribenzoate

1989 ◽  
Vol 262 (1) ◽  
pp. 83-89 ◽  
Author(s):  
K J Föhr ◽  
J Scott ◽  
G Ahnert-Hilger ◽  
M Gratzl
Keyword(s):  
Endocrine Cells ◽  
Calcium Release ◽  
Cell Types ◽  
Inhibitory Effect ◽  
Maximal Effect ◽  
Thiol Compounds ◽  
Inositol 1,4,5 Trisphosphate ◽  
Dependent Inhibition ◽  
Pheochromocytoma Pc12 ◽  
First Time

The inositol 1,4,5-trisphosphate (IP3)-sensitive Ca2+ compartment of endocrine cells was studied with alpha-toxin- and digitonin-permeabilized rat insulinoma (RINA2) and rat pheochromocytoma (PC12) cells. The Ca2+ uptake was ATP-dependent, and submicromolar concentrations of IP3 specifically released the stored Ca2+. Half-maximal Ca2+ release was observed with 0.25-0.5 mumol of IP3/l, and the amount of Ca2+ released due to IP3 could be enhanced by additional loading of the Ca2+ compartment. Consecutive additions of the same concentration of IP3 for 1-2 h always released the same amount of Ca2+ without desensitization, providing an ideal basis to further characterize the IP3-induced Ca2+ release. Here we describe for the first time a reversible inhibitory effect of decavanadate on the IP3-induced Ca2+ release. Among the vanadium species tested (decavanadate, oligovanadate and monovanadate), only decavanadate was inhibitory, with a half-maximal effect at 5 mumol/l in both cell types. The effect of decavanadate could be overcome by increasing the amount of sequestered Ca2+ or added IP3. Decavanadate did not affect the ATP-driven Ca2+ uptake but oligovanadate was inhibitory on Ca2+ uptake. p-Hydroxymercuribenzoate (pHMB) at concentrations between 10 and 30 mumol/l also inhibited the Ca2+ release due to IP3. Thiol compounds such as dithiothreitol (DTT; 1 mmol/l) added before pHMB removed all its inhibitory effect on the IP3-induced Ca2+ release, whereas the inhibition caused by decavanadate was unaffected by DTT. Thus, the decavanadate-dependent inhibition functions by a distinctly different mechanism than pHMB and could serve as a specific tool to analyse various aspects of the IP3-induced Ca2+ release within endocrine cells.

Human kidney 11β-hydroxysteroid dehydrogenase: regulation by adrenocorticotropin?

1996 ◽  
Vol 134 (3) ◽  
pp. 301-307 ◽  
Author(s):  
S Diederich ◽  
M Quinkler ◽  
K Miller ◽  
P Heilmann ◽  
M Schöneshöfer ◽  
...  
Keyword(s):  
Human Kidney ◽  
Kinetic Studies ◽  
Hydroxysteroid Dehydrogenase ◽  
Inhibitory Effect ◽  
Benjamin Franklin ◽  
Dependent Inhibition ◽  
Direct Inhibitory Effect ◽  
Dose Dependent Inhibition ◽  
Endogenous Substrates ◽  
Radioactive Detection

Diederich S, Quinkler M, Miller K, Heilmann P, Schöneshöfer M, Oelkers W. Human kidney 11βhydroxysteroid dehydrogenase: regulation by adrenocorticotropin? Eur J Endocrinol 1996;134:301–7. ISSN 0804–4643 In ectopic adrenocorticotropin (ACTH) syndrome (EAS) with higher ACTH levels than in pituitary Cushing's syndrome and during ACTH infusion, the ratio of cortisol to cortisone in plasma and urine is increased, suggesting inhibition of renal 11β-hydroxysteroid dehydrogenase (11β-HSD) by ACTH or by ACTH-dependent steroids. Measuring the conversion of cortisol to cortisone by human kidney slices under different conditions, we tested the possibility of 11β-HSD regulation by ACTH and corticosteroids. Slices prepared from unaffected parts of kidneys removed because of renal cell carcinoma were incubated with unlabeled or labeled cortisol, and cortisol and cortisone were quantitated after HPLC separation by UV or radioactive detection. The 11β-HSD activity was not influenced by incubation with increasing concentrations (10−12–10−9 mol/l) of ACTH (1–24 or 1–39) for 1 h. Among 12 ACTH-dependent steroids tested (10−9–10−6 mol/l), only corticosterone (IC50 = 2 × 10−7 mol/l), 18-OH-corticosterone and 11βOH-androstenedione showed a significant dose-dependent inhibition of 11β-HSD activity. The percentage conversion rate of cortisol to cortisone was concentration dependent over the whole range of cortisol concentrations tested (10−8–10−5 mol/l). A direct inhibitory effect of ACTH on 11β-HSD is, therefore, unlikely. The only steroids inhibiting the conversion of cortisol to cortisone are natural substrates for 11β-HSD Kinetic studies show a saturation of the enzyme at high cortisol concentrations. Thus, the reduced percentage renal cortisol inactivation in EAS seems to be due mainly to overload of the enzyme with endogenous substrates (cortisol, corticosterone and others) rather than to direct inhibition of 11β-HSD by ACTH or ACTHdependent steroids, not being substrates of 11β-HSD. S Diederich, Department of Endocrinology, Klinikum Benjamin Franklin, Freie Universität Berlin, Hindenburgdamm 30, 12200 Berlin, Germany

Nitric oxide mediates the neural nonadrenergic, noncholinergic relaxation of pig tracheal smooth muscle

1992 ◽  
Vol 262 (4) ◽  
pp. L511-L514 ◽  
Author(s):  
M. S. Kannan ◽  
D. E. Johnson
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Electrical Field Stimulation ◽  
Selective Inhibition ◽  
Inhibitory Effect ◽  
Isometric Tension ◽  
Tracheal Smooth Muscle ◽  
Basal Tone ◽  
Dependent Inhibition ◽  
Nanc Relaxation

In pig tracheal smooth muscle, the isometric tension responses to electrical field stimulation (EFS) were studied after raising the tone with carbamylcholine chloride (carbachol). EFS induced frequency-dependent relaxations that were nonadrenergic, noncholinergic (NANC) in nature. Addition of NG-nitro-L-arginine (L-NOArg), an inhibitor of nitric oxide (NO) synthesis from L-arginine, resulted in concentration-dependent inhibition of the relaxation response to EFS. Pretreatment of the tissues with L-arginine (1 mM) prevented the inhibitory effect of L-NOArg on the EFS-induced relaxations at the frequencies studied. However, in the presence of D-arginine, EFS-induced relaxations were inhibited by L-NOArg. L-Arginine, D-arginine, and L-NOArg had no significant effects on basal tone of the muscle. In the presence of L-NOArg, vasoactive intestinal polypeptide (3 x 10(-7) M), the nicotinic agonist dimethylphenyl piperazinium bromide (100 microM), and isoproterenol (1 microM) relaxed carbachol-induced tone. The concentration-dependent selective inhibition of neural relaxation by L-NOArg and its reversal by L-arginine in a stereospecific manner are consistent with NO-mediated NANC relaxation of pig tracheal smooth muscle.

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.

Apolipoprotein AIV: a potent endogenous inhibitor of lipid oxidation

1998 ◽  
Vol 274 (5) ◽  
pp. H1836-H1840 ◽  
Author(s):  
Xiaofa Qin ◽  
Debi K. Swertfeger ◽  
Shuqin Zheng ◽  
David Y. Hui ◽  
Patrick Tso
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Inhibitory Effect ◽  
Lipoprotein Oxidation ◽  
Atherogenic Lipid Profile ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Endogenous Antioxidant ◽  
Knockout Animals

Overexpression of apolipoprotein (apo) AIV in transgenic mice confers significant protection against atherosclerosis in apoE knockout animals even in the presence of a more severe atherogenic lipid profile. Because lipoprotein oxidation has been recognized to be pivotal in development of atherosclerosis, the antioxidative activity of apoAIV was investigated. Fasting intestinal lymph was used to mimic conditions in the interstitial fluid, the potential site for lipoprotein oxidation in vivo. ApoAIV (10 μg/ml) significantly inhibited copper-mediated oxidation of lymph. This inhibitory effect was further evaluated using purified low-density lipoprotein. Addition of apoAIV (2.5 μg/ml) increased the time of 50% conjugated diene formation by 2.4-fold, whereas apoE or BSA did not show such a protection even at 20 μg/ml. Addition of apoAIV during the propagation phase also resulted in a dose-dependent inhibition. ApoAIV also protected macrophage-induced oxidation of fasting lymph. These results provide the first evidence that apoAIV is a potent endogenous antioxidant.

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