Inhibitory Effect of Fentanyl on Acetylcholine-induced Relaxation in Rat Aorta

2004 ◽  
Vol 101 (1) ◽  
pp. 89-96 ◽  
Author(s):  
Ju-Tae Sohn ◽  
Seong-Ho Ok ◽  
Hee-Jin Kim ◽  
Seon-Hak Moon ◽  
Il-Woo Shin ◽  
...  
Keyword(s):  
Muscarinic Receptor ◽  
Response Curve ◽  
Calcium Ionophore ◽  
Receptor Activation ◽  
Inhibitory Effect ◽  
Rat Aorta ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
Acetylcholine Concentration ◽  
Concentration Response Curve

Background Previous study has shown that fentanyl attenuates acetylcholine-induced vasorelaxation. The goal of the current in vitro study was to identify the muscarinic receptor subtype that is mainly involved in the fentanyl-induced attenuation of endothelium-dependent relaxation elicited by acetylcholine. Methods The effects of fentanyl and muscarinic receptor antagonists on the acetylcholine concentration-response curve were assessed in aortic vascular smooth muscle ring preparations precontracted with phenylephrine. In the rings pretreated independently with pirenzepine, 4-diphenylacetoxyl-N-methylpiperidine methiodide, and naloxone, acetylcholine concentration-response curves were generated in the presence and absence of fentanyl. The effect of fentanyl on the concentration-response curve for calcium ionophore A23187 was assessed. Results Fentanyl (0.297 x 10 0.785 x 10 m) attenuated acetylcholine-induced vasorelaxation in ring preparations with or without 10 m naloxone. Pirenzepine (10 to 10 m) and 4-diphenylacetoxyl-N-methylpiperidine methiodide (10 to 10 m) produced a parallel rightward shift in the acetylcholine concentration-response curve. The concentrations (-log M) of pirenzepine and 4-diphenylacetoxyl-N-methylpiperidine methiodide necessary to displace the concentration-response curve of an acetylcholine by twofold were estimated to be 6.886 +/- 0.070 and 9.256 +/- 0.087, respectively. Methoctramine, 10 m, did not alter the acetylcholine concentration-response curve. Fentanyl, 0.785 x 10 m, attenuated acetylcholine-induced vasorelaxation in the rings pretreated with 10 m pirenzepine but had no effect on vasorelaxation in the rings pretreated with 10 m 4-diphenylacetoxyl-N-methylpiperidine methiodide. Fentanyl, 0.785 x 10 m, did not significantly alter calcium ionophore A23187-induced vasorelaxation. Conclusions These results indicate that fentanyl attenuates acetylcholine-induced vasorelaxation via an inhibitory effect at a level proximal to nitric oxide synthase activation on the pathway involving endothelial M3 muscarinic receptor activation in rat aorta.

Effects of glucocorticoids on prostaglandin formation by human amnion

1990 ◽  
Vol 68 (6) ◽  
pp. 671-676 ◽  
Author(s):  
William Gibb ◽  
Jean-Claude Lavoie
Keyword(s):  
Calcium Ionophore ◽  
Inhibitory Effect ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
Isolated Cells ◽  
Stimulatory Action ◽  
Human Amnion ◽  
Human Labor ◽  
Epidermal Growth

The human amnion may be an important source of prostaglandins involved in the onset of human labor and therefore it is important to define the factors that regulate their formation in this tissue. In the present study we demonstrate that glucocorticoids inhibit prostaglandin production by freshly isolated amnion cells. The inhibitory action of the glucocorticoids, however, changes to a stimulatory action when the cells are maintained in primary culture for a few days. For both inhibition and stimulation, concentrations of 10−8 M dexamethasone or greater were required to give significant effects, and estradiol and progesterone had no effect on the prostaglandin output of the cells. Epidermal growth factor (EGF), which has previously been found to stimulate prostaglandin output by confluent amnion cells, did not alter prostaglandin output of cells initially placed in culture. Furthermore, the stimulatory action of EGF and dexamethasone appeared additive. The calcium ionophore A23187 stimulated prostaglandin output in freshly isolated cells and accentuated the inhibitory effect of dexamethasone. These studies indicate that prostaglandin formation by human amnion during pregnancy could be regulated by glucocorticoids. These steroids are easily available to the amnion by way of cortisone conversion to Cortisol by the maternal decidua. The results also indicate that amnion is capable of responding to glucocorticoids in both a stimulatory and inhibitory fashion and whether one or both actions are of importance in vivo is a question that is as yet unresolved.Key words: prostaglandins, amnion, fetal membranes, glucocorticoids, labor, pregnancy.

Mitogenesis by serum and PDGF is independent of PI degradation and PKC in VSMC

1989 ◽  
Vol 256 (4) ◽  
pp. C886-C892 ◽  
Author(s):  
M. Kihara ◽  
P. J. Robinson ◽  
S. H. Buck ◽  
R. C. Dage
Keyword(s):  
Growth Factor ◽  
Cell Growth ◽  
Growth Control ◽  
Calcium Ionophore ◽  
Rat Aorta ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
Pi Turnover ◽  
Fetal Bovine ◽  
20 Nm

Capacities of serum, platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF) on phosphatidylinositol (PI) degradation and cell growth were compared in cultured vascular smooth muscle cells (VSMC) from rat aorta. The role of protein kinase C (PKC) in growth control was also evaluated using polymixin B, a selective inhibitor of PKC. Both dialyzed and nondialyzed fetal bovine serum (FBS) in concentrations from 2 to 20% stimulated [3H]thymidine incorporation into DNA and cell growth without producing corresponding increases in PI turnover. Moreover, both PDGF (40-160 ng/ml) and FGF (6.25-150 ng/ml) also stimulated mitogenesis, but PDGF was more effective although less potent. Mitogenic amounts of PDGF did not stimulate PI turnover, whereas a maximally mitogenic amount of FGF (50 ng/ml) did produce a slight increase. Polymixin B inhibited PKC activity (IC50, 32 microM) from these cells but failed to suppress DNA synthesis produced by 10% FBS or PDGF (50 ng/ml). However, it did suppress that by FGF (50 ng/ml). Angiotensin II (10(-11)-10(-7) M) and phorbol 12,13-dibutyrate (PDB, 1-20 nM) were not mitogenic in the presence or absence of insulin (10 micrograms/ml) or the calcium ionophore A23187 (0.25-4 microM), under serum-free conditions. Instead, PDB inhibited mitogenesis of cells maintained under 0.2% FBS or stimulated with insulin (10 micrograms/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibitory Effects of Etomidate and Ketamine on Endothelium-dependent Relaxation in Canine Pulmonary Artery

2001 ◽  
Vol 94 (4) ◽  
pp. 668-677 ◽  
Author(s):  
Koji Ogawa ◽  
Satoru Tanaka ◽  
Paul A. Murray
Keyword(s):  
Pulmonary Artery ◽  
Calcium Ionophore ◽  
Receptor Activation ◽  
Isometric Tension ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
Inhibitory Effects ◽  
Pulmonary Arterial ◽  
Synthase Inhibitor ◽  
Endothelium Dependent Relaxation

Background The authors recently demonstrated that acetylcholine-induced pulmonary vasorelaxation had two primary components, nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF). The goal was to investigate the effects of etomidate and ketamine on the NO- and EDHF-mediated components of pulmonary vasorelaxation in response to acetylcholine, bradykinin, and the calcium ionophore, A23187. Methods Canine pulmonary arterial rings with an intact endothelium were suspended in organ chambers for isometric tension recording. The effects of etomidate and ketamine (10(-5) M and 10(-4) M) on vasorelaxation responses to acetylcholine, bradykinin, and A23187 were assessed in phenylephrine-contracted rings. The NO- and EDHF-mediated components of relaxation were assessed using a NO synthase inhibitor (N-nitro-L-arginine methylester [L-NAME]: 10(-4) M) and a Ca2+-activated potassium channel inhibitor (tetrabutylammonium hydrogen sulfate [TBA]: 10(-3) M) in rings pretreated with a cyclooxygenase inhibitor (ibuprofen: 10(-5) M). Intracellular calcium concentration ([Ca2+]i) was measured in cultured bovine pulmonary artery endothelial cells loaded with acetoxylmethyl ester of fura-2. Results Etomidate and ketamine attenuated pulmonary vasorelaxation in response to acetylcholine and bradykinin, whereas they had no effect on the response to A23187. The relaxant responses to acetylcholine and bradykinin were attenuated by L-NAME or TBA alone and were abolished by combined inhibition in rings pretreated with ibuprofen. Etomidate and ketamine further attenuated both L-NAME-resistant and TBA-resistant relaxation. These anesthetics also inhibited increases in endothelial [Ca2+]i in response to bradykinin, but not A23187. Conclusion These results indicate that etomidate and ketamine attenuated vasorelaxant responses to acetylcholine and bradykinin by inhibiting both NO- and EDHF-mediated components. Moreover, our results suggest that these anesthetics do not directly suppress NO or EDHF activity, but rather inhibit the endothelial [Ca2+]i transient in response to receptor activation.

Singlet oxygen scavengers affect laser-dye impairment of endothelium-dependent responses of brain arterioles

1996 ◽  
Vol 270 (4) ◽  
pp. H1258-H1263 ◽  
Author(s):  
W. I. Rosenblum ◽  
G. H. Nelson
Keyword(s):  
Singlet Oxygen ◽  
Calcium Ionophore ◽  
Inhibitory Effect ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
Protective Effects ◽  
Laser Dye ◽  
Oxygen Scavengers ◽  
Heat Injury

This study investigates the possible role of singlet oxygen in accounting for the inhibitory effect of laser-dye injury on endothelium-dependent dilations. The combination of helium-neon (HeNe) laser (20-s exposure) and intravascular Evans blue impairs endothelium-dependent dilation of mouse pial arterioles by acetylcholine (ACh), bradykinin (BK), and calcium ionophore A23187. Each has a different endothelium-derived mediator (EDRFACh, EDRFBK, EDRFionophore, respectively). In this study, diameters at a craniotomy site were monitored in vivo with an image splitter-television microscope. The laser-dye injury, as usual, abolished the responses 10 and 30 min after injury, with recovery, complete or partial, at 60 min. Dilations by sodium nitroprusside, an endothelium-independent dilator, were not affected by laser-dye. When the singlet oxygen scavengers L-histidine (10(-3) M) and L-tryptophan (10(-2) M) were added to the suffusate over the site, the responses to ACh at 10 and 30 min were relatively intact, the response to BK was partly protected at 10 min only, and the response to ionophore was still totally impaired at 10 and 30 min. Lysine, a nonscavenging amino acid, had no protective effects with any dilator. We postulate that a heat-induced injury initiates a chain of events resulting in prolonged singlet oxygen generation by the endothelial cell (not by the dye). We postulate further that destruction of EDRFACh by singlet oxygen is responsible for laser-dye inhibition of ACh and that generation of the radical must continue for > or = 30 min. On the other hand, the heat injury itself is probably responsible for the elimination of the response to ionophore. Heat plus singlet oxygen generated by heat-damaged tissue may initially impair the response to BK, but by 30 min only the effects of some other factor, presumably heat injury, account for the impaired response to BK.

Calcium modulates vasopressin effect in rabbit cortical collecting tubule

1987 ◽  
Vol 252 (1) ◽  
pp. F115-F121 ◽  
Author(s):  
M. A. Dillingham ◽  
B. S. Dixon ◽  
R. J. Anderson
Keyword(s):  
Calcium Uptake ◽  
Calcium Ionophore ◽  
Inhibitory Effect ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
Calcium Activity ◽  
Cellular Calcium ◽  
Collecting Tubules ◽  
Bathing Fluid

The calcium ion has been proposed to be an important mediator of the hydroosmotic response to arginine vasopressin (AVP). We examined the effect of reducing basolateral calcium activity on hydraulic conductivity (Lp) in response to AVP in rabbit cortical collecting tubules (CCT) perfused in vitro. Each tubule served as its own control. Reducing bathing fluid calcium from 0.94 mM to 4.6 microM reduced Lp in each tubule (mean decrease from 146 +/- 13 to 106 +/- 7 cm X s-1 X atm X 10(-7), n = 11, P less than 0.025). To determine whether this inhibitory effect was due to a decrease in cellular calcium uptake, we measured the effect of adding 10(-4) M lanthanum to bathing fluid on AVP-stimulated Lp. Lanthanum decreased Lp (from 109 +/- 13 to 80 +/- 10 cm X s-1 X atm X 10(-7), P less than 0.05) in each tubule. To examine the site at which low peritubular calcium activity regulates AVP action, we measured the effect of decreasing bathing fluid calcium on 8-[p-chlorophenylthio]-adenosine 3',5'-cyclic monophosphate (ClPheS-cAMP)-stimulated Lp (n = 5). Decreasing bathing fluid calcium significantly decreases (P less than 0.025) Lp response to ClPheS-cAMP. Since these results suggest that cellular calcium uptake can exert a post-cAMP effect to modulate AVP action, we examined the effect of the calcium ionophore A23187 (10(-7) M) on AVP- and ClPheS-cAMP-stimulated Lp A23187 reversibly potentiates (25-30%, P less than 0.025) the Lp response to both AVP and ClPheS-cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibitory effects of calcium ionophore pretreatment of porcine oocytes on polyspermic fertilization

Zygote ◽  
2006 ◽  
Vol 14 (1) ◽  
pp. 17-22 ◽  
Author(s):  
T. Hayashi ◽  
H. Sato ◽  
H. Iwata ◽  
T. Kuwayama ◽  
Y. Monji
Keyword(s):  
Calcium Ionophore ◽  
Inhibitory Effect ◽  
Calcium Ionophore A23187 ◽  
The Other ◽  
Ionophore A23187 ◽  
Inhibitory Effects ◽  
High Concentration ◽  
Maturation Period ◽  
Low Concentration ◽  
Other Hand

The present study examined the inhibitory effects of various pretreatment concentrations (0–100 μM) of the calcium ionophore A23187 on polyspermic fertilization and then examined the effect of the maturation period and the time between calcium ionophore treatment and fertilization on the inhibitory effect of calcium ionophore on polyspermic fertilization. In experiment 1, a high concentration of calcium ionophore (100 μM) increased the rate of activated oocytes, but the rate of fertilization declined. On the other hand, when oocytes were treated with a low concentration of calcium ionophore (10 μM), monospermic fertilization was significantly increased (10 μM; 31.3%) (p < 0.05). In experiment 2, oocytes were cultured for various times (0, 0.5, 3, 6 h) after calcium ionophore treatment (10 μM) before fertilization. The highest rate of monospermic fertilization was detected in the oocytes cultured for 6 h after calcium ionophore treatment before fertilization. In experiments 3 and 4, we examined the effect of the maturation period (40 h or 44 h) on the rate of fertilization and blastulation of oocytes pretreated with calcium ionophore. The treatment of oocytes with calcium ionophore significantly decreased the rate of polyspermic fertilization regardless of the maturation period (44 h: with calcium ionophore 26.25% vs without 78.8%; 40 h: with calcium ionophore 37.5% vs without 77.5%); however, calcium ionophore treatment increased the rates of monospermic fertilization and blastulation of the oocytes matured for 44 h, but not those matured for 40 h. In conclusion, activation with a low concentration of calcium ionophore (10 μM) and a further 6 h of culture before fertilization improved the rate of monospermic fertilization and blastulation.

scholarly journals Inhibitory effect of LY 255283 on the synthesis of leukotriene B4and thromboxane A2in human peripheral blood polymorphonuclear leukocytes and monocytes

1993 ◽  
Vol 2 (6) ◽  
pp. 407-409 ◽  
Author(s):  
M. Ugur ◽  
M. Melli
Keyword(s):  
Receptor Antagonist ◽  
Peripheral Blood ◽  
Polymorphonuclear Leukocytes ◽  
Human Peripheral Blood ◽  
Calcium Ionophore ◽  
Inhibitory Effect ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
Human Monocytes

LY 255283 [(1-(5-ethyl-2-hydroxy-4-(6-methyl-6-)1H-tetrazol-5-yl)-heptyloxy) phenyl)ethanone], a specific leukotriene B4(LTB4) receptor antagonist, inhibited the production of LTB4in human peripheral blood polymorphonuclear leukocytes (PMNL) and in monocytes activated by calcium ionophore A23187. In human monocytes activated by ionophore it inhibited also the production of thromboxane B2(TXB2). The effect of LY 255283 on 5-lipoxygenase (5-LO) and LTA4hydrolase activities which catalyse the production of LTB4and LTA4has not been studied yet. It is thought that LY 255283 may inhibit the production of LTB4and TXA2by antagonising the effect of ionophore-induced LTB4on 5-lipoxygenase and cyclooxygenase in human peripheral blood PMNL and monocytes.

Heparin inhibits histamine release from canine mast cells

1993 ◽  
Vol 264 (4) ◽  
pp. L387-L390 ◽  
Author(s):  
N. Inase ◽  
R. E. Schreck ◽  
S. C. Lazarus
Keyword(s):  
Mast Cells ◽  
Charge Density ◽  
Histamine Release ◽  
Negative Charge ◽  
Calcium Ionophore ◽  
Inhibitory Effect ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
Similar Inhibitory Effect ◽  
Negative Charge Density

To determine the role of heparin in mast cell exocytosis, we studied the effect of heparin on histamine release induced by compound 48/80 or calcium ionophore A23187 in canine mastocytoma cells (BR). Heparin caused concentration-dependent inhibition of compound 48/80-induced histamine release from mast cells (n = 4; P < 0.05) with a mean inhibitory concentration of 0.14 +/- 0.01 U/ml (mean +/- SE). Mean maximal inhibition was 69.3 +/- 2.0%. In contrast, heparin had no effect on calcium ionophore A23187-induced histamine release. Although benzyl alcohol, a preservative of pharmaceutical heparin, had no effect, purified heparin produced a similar inhibitory effect on compound 48/80-induced histamine release (n = 4; P < 0.05). The inhibitory effect of heparin on histamine release was rapid and was eliminated by washing cells. Dextran sulfate, a polysaccharide with negative charge density, produced a similar inhibitory effect on compound 48/80-induced histamine release (n = 4; P < 0.05). We conclude that heparin inhibits compound 48/80-induced exocytosis in mast cells probably by its negative charge density.

scholarly journals Binding of monoclonal antibody AA4 to gangliosides on rat basophilic leukemia cells produces changes similar to those seen with Fc epsilon receptor activation.

1992 ◽  
Vol 116 (3) ◽  
pp. 635-646 ◽  
Author(s):  
C Oliver ◽  
N Sahara ◽  
S Kitani ◽  
A R Robbins ◽  
L M Mertz ◽  
...  
Keyword(s):  
Histamine Release ◽  
Calcium Ionophore ◽  
Receptor Activation ◽  
Calcium Ionophore A23187 ◽  
Rat Tissues ◽  
Ionophore A23187 ◽  
Ige Receptor ◽  
Culture Dish ◽  
Basophilic Leukemia

The mAb AA4 binds to novel derivatives of the ganglioside Gd1b on rat basophilic leukemia (RBL-2H3) cells. Some of the gangliosides are located close to the high affinity IgE receptor (Fc epsilon RI), and binding of mAb AA4 inhibits Fc epsilon RI-mediated histamine release. In the present study, mAb AA4 was found to bind exclusively to mast cells in all rat tissues examined. In vitro, within 1 min of mAb AA4 binding, the cells underwent striking morphologic changes. They lost their normal spindle shaped appearance, increased their ruffling, and spread over the surface of the culture dish. These changes were accompanied by a redistribution of the cytoskeletal elements, actin, tubulin, and vimentin, but only the actin was associated with the membrane ruffles. Binding of mAb AA4 also induces a rise in intracellular calcium, stimulates phosphatidyl inositol breakdown, and activates PKC. However, the extent of these changes was less than that observed when the cells were stimulated with antigen or antibody directed against the Fc epsilon RI. None of these changes associated with mAb AA4 binding were seen when the cells were exposed to nonspecific IgG, IgE, or four other anti-cell surface antibodies, nor were the changes induced by binding mAb AA4 at 4 degrees C or in the absence of extracellular calcium. Although mAb AA4 does not stimulate histamine release, it enhances the effect of the calcium ionophore A23187 mediated release. The morphological and biochemical effects produced by mAb AA4 are similar to those seen following activation of the cell through the IgE receptor. Therefore, the surface gangliosides which bind mAb AA4 may function in modulating secretory events.

Endothelial dysfunction is induced by proinflammatory oxidant hypochlorous acid

2001 ◽  
Vol 281 (4) ◽  
pp. H1469-H1475 ◽  
Author(s):  
Chunxiang Zhang ◽  
Rakesh Patel ◽  
Jason P. Eiserich ◽  
Fen Zhou ◽  
Stacey Kelpke ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Hypochlorous Acid ◽  
Tissue Injury ◽  
Calcium Ionophore ◽  
Aortic Ring ◽  
Inhibitory Effect ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
Sprague Dawley ◽  
Inflammatory Conditions

The myeloperoxidase (MPO)-derived oxidant hypochlorous acid (HOCl) plays a role in tissue injury under inflammatory conditions. The present study tests the hypothesis that HOCl decreases nitric oxide (NO) bioavailability in the vasculature of Sprague-Dawley rats. Aortic ring segments were pretreated with HOCl (1–50 μM) followed by extensive washing. Endothelium-dependent relaxation was then assessed by cumulative addition of acetylcholine (ACh) or the calcium ionophore A23187 . HOCl treatment significantly impaired both ACh- and A23187 -mediated relaxation. In contrast, endothelium-independent relaxation induced by sodium nitroprusside was unaffected. The inhibitory effect of HOCl on ACh-induced relaxation was reversed by exposure of ring segments to l-arginine but notd-arginine. In cellular studies, HOCl did not alter endothelial NO synthase (NOS III) protein or activity, but inhibited formation of the NO metabolites nitrate (NO[Formula: see text]) and nitrite (NO[Formula: see text]). The reduction in total NO metabolite production in bovine aortic endothelial cells was also reversed by addition of l-arginine. These data suggest that HOCl induces endothelial dysfunction via modification ofl-arginine.

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