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  1. Article: Potentiation of anandamide effects in mesenteric beds isolated from endotoxemic rats.

    Orliac, María Luz / Peroni, Roxana / Celuch, Stella M / Adler-Graschinsky, Edda

    The Journal of pharmacology and experimental therapeutics

    2003  Volume 304, Issue 1, Page(s) 179–184

    Abstract: The aim of the present experiments was to study the effects of exogenously added anandamide on transient norepinephrine (NE)-induced contractions in mesenteric beds isolated from adult male Sprague-Dawley rats 6 h after the i.p. administration of 5 mg kg( ...

    Abstract The aim of the present experiments was to study the effects of exogenously added anandamide on transient norepinephrine (NE)-induced contractions in mesenteric beds isolated from adult male Sprague-Dawley rats 6 h after the i.p. administration of 5 mg kg(-1) lipopolysaccharide (LPS). LPS treatment induced a 3-fold increase in total nitric-oxide synthase (NOS) activity without modifying either the systolic blood pressure or the vascular reactivity to NE of the isolated mesenteric bed. The endocannabinoid anandamide (0.01-10 microM) caused concentration-dependent reductions of the contractile responses to NE in the isolated mesenteric bed. This effect was significantly potentiated after LPS treatment compared with the controls. Anandamide-induced reductions of the contractile responses to NE in mesenteric beds isolated from LPS-treated rats were unmodified by endothelium removal but significantly diminished by either the anandamide amidase inhibitor phenylmethylsulfonyl fluoride (200 microM) or the vanilloid receptor antagonist capsazepine (1 microM). The vanilloid receptor agonist capsaicin (0.01-100 nM) also caused concentration-dependent relaxations that were potentiated in mesenteric beds from LPS-treated rats. Nevertheless, they were unmodified by 1 microM capsazepine. It is concluded that the potentiation of anandamide relaxations after LPS treatment, which are evident at early stages of endotoxic shock, could involve the participation of an anandamide metabolite and might be mediated, at least in part, through a vanilloid receptor.
    MeSH term(s) Amidohydrolases/antagonists & inhibitors ; Animals ; Arachidonic Acids/antagonists & inhibitors ; Arachidonic Acids/pharmacology ; Blood Pressure/drug effects ; Cannabinoid Receptor Modulators ; Capsaicin/pharmacology ; Endocannabinoids ; Endotoxemia/physiopathology ; Enzyme Inhibitors/pharmacology ; Lipopolysaccharides/pharmacology ; Male ; Muscle Relaxation/drug effects ; Muscle, Smooth, Vascular/drug effects ; Nitric Oxide Synthase/metabolism ; Nitric Oxide Synthase Type III ; Norepinephrine/antagonists & inhibitors ; Norepinephrine/pharmacology ; Phenylmethylsulfonyl Fluoride/pharmacology ; Polyunsaturated Alkamides ; Rats ; Rats, Sprague-Dawley ; Receptors, Drug/antagonists & inhibitors ; Shock, Septic/drug therapy ; Shock, Septic/physiopathology ; Splanchnic Circulation/drug effects ; Vasoconstrictor Agents/antagonists & inhibitors ; Vasoconstrictor Agents/pharmacology
    Chemical Substances Arachidonic Acids ; Cannabinoid Receptor Modulators ; Endocannabinoids ; Enzyme Inhibitors ; Lipopolysaccharides ; Polyunsaturated Alkamides ; Receptors, Drug ; Vasoconstrictor Agents ; Phenylmethylsulfonyl Fluoride (57KD15003I) ; Nitric Oxide Synthase (EC 1.14.13.39) ; Nitric Oxide Synthase Type III (EC 1.14.13.39) ; Nos3 protein, rat (EC 1.14.13.39) ; Amidohydrolases (EC 3.5.-) ; arachidonoylethanolamide synthase (EC 3.5.1.-) ; Capsaicin (S07O44R1ZM) ; anandamide (UR5G69TJKH) ; Norepinephrine (X4W3ENH1CV)
    Language English
    Publishing date 2003-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3106-9
    ISSN 1521-0103 ; 0022-3565
    ISSN (online) 1521-0103
    ISSN 0022-3565
    DOI 10.1124/jpet.102.041095
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Anandamide elicits an acute release of nitric oxide through endothelial TRPV1 receptor activation in the rat arterial mesenteric bed.

    Poblete, Inés M / Orliac, María Luz / Briones, René / Adler-Graschinsky, Edda / Huidobro-Toro, J Pablo

    The Journal of physiology

    2005  Volume 568, Issue Pt 2, Page(s) 539–551

    Abstract: In the isolated rat mesenteric bed, the 1 min perfusion with 100 nm anandamide, a concentration that did not evoke vasorelaxation, elicited an acute release of 165.1 +/- 9.2 pmol nitric oxide (NO) that was paralleled by a 2-fold increase in cGMP tissue ... ...

    Abstract In the isolated rat mesenteric bed, the 1 min perfusion with 100 nm anandamide, a concentration that did not evoke vasorelaxation, elicited an acute release of 165.1 +/- 9.2 pmol nitric oxide (NO) that was paralleled by a 2-fold increase in cGMP tissue levels. The rise in NO released was mimicked by either (R)-(+)-methanandamide or the vanilloid receptor agonists resiniferatoxin and (E)-capsaicin but not by its inactive cis-isomer (Z)-capsaicin. The NO release elicited by either anandamide or capsaicin was reduced by the TRPV1 receptor antagonists 5'-iodoresiniferatoxin, SB 366791 and capsazepine as well as by the cannabinoid CB(1) receptor antagonists SR 141716A or AM251. The outflow of NO elicited by anandamide and capsaicin was also reduced by endothelium removal or NO synthase inhibition, suggesting the specific participation of endothelial TRPV1 receptors, rather than the novel endothelial TRPV4 receptors. Consistently, RT-PCR showed the expression of the mRNA coding for the rat TRPV1 receptor in the endothelial cell layer, in addition to its expression in sensory nerves. The participation of sensory nerves on the release of NO was precluded on the basis that neonatal denervation of the myenteric plexus sensory nerves did not modify the pattern of NO release induced by anandamide and capsaicin. We propose that low concentrations of anandamide, devoid of vasorelaxing effects, elicit an acute release of NO mediated predominantly by the activation of endothelial TRPV1 receptors whose physiological significance remains elusive.
    MeSH term(s) Anilides/pharmacology ; Animals ; Arachidonic Acids/pharmacology ; Cannabinoid Receptor Antagonists ; Capsaicin/analogs & derivatives ; Capsaicin/pharmacology ; Cinnamates/pharmacology ; Cyclic GMP/metabolism ; Diterpenes/pharmacology ; Dose-Response Relationship, Drug ; Endocannabinoids ; Endothelium, Vascular/drug effects ; Endothelium, Vascular/metabolism ; In Vitro Techniques ; Male ; Mesenteric Artery, Superior/drug effects ; Mesenteric Artery, Superior/metabolism ; Nitric Oxide/metabolism ; Nitroarginine/pharmacology ; Perfusion ; Piperidines/pharmacology ; Polyunsaturated Alkamides ; Pyrazoles/pharmacology ; RNA, Messenger/analysis ; Rats ; Rats, Sprague-Dawley ; TRPV Cation Channels/drug effects ; TRPV Cation Channels/genetics ; TRPV Cation Channels/metabolism ; Vasodilation/drug effects
    Chemical Substances Anilides ; Arachidonic Acids ; Cannabinoid Receptor Antagonists ; Cinnamates ; Diterpenes ; Endocannabinoids ; N-(3-methoxyphenyl)-4-chlorocinnamanilide ; Piperidines ; Polyunsaturated Alkamides ; Pyrazoles ; RNA, Messenger ; TRPV Cation Channels ; Trpv2 protein, rat ; methanandamide (150314-39-9) ; Nitroarginine (2149-70-4) ; Nitric Oxide (31C4KY9ESH) ; resiniferatoxin (A5O6P1UL4I) ; Cyclic GMP (H2D2X058MU) ; capsazepine (LFW48MY844) ; rimonabant (RML78EN3XE) ; Capsaicin (S07O44R1ZM) ; anandamide (UR5G69TJKH)
    Language English
    Publishing date 2005-10-15
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3115-x
    ISSN 1469-7793 ; 0022-3751
    ISSN (online) 1469-7793
    ISSN 0022-3751
    DOI 10.1113/jphysiol.2005.094292
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Increases in vanilloid TRPV1 receptor protein and CGRP content during endotoxemia in rats.

    Orliac, María Luz / Peroni, Roxana N / Abramoff, Tamara / Neuman, Isabel / Podesta, Ernesto J / Adler-Graschinsky, Edda

    European journal of pharmacology

    2007  Volume 566, Issue 1-3, Page(s) 145–152

    Abstract: The aim of the present study was to determine whether the transient receptor potential vanilloid (TRPV1) receptor protein as well as the calcitonin gene-related peptide (CGRP) content could be enhanced after the i.p. administration of 5 mg/kg ... ...

    Abstract The aim of the present study was to determine whether the transient receptor potential vanilloid (TRPV1) receptor protein as well as the calcitonin gene-related peptide (CGRP) content could be enhanced after the i.p. administration of 5 mg/kg lipopolysaccharide (LPS) to Sprague-Dawley rats. In tongue tissue, used as a representative model of TRPV1 receptors expression, there was a significant increase in the abundance of TRPV1 receptor protein 6 h after LPS administration. In mesenteric arteries, the density of the CGRP-positive nerves as well as the release of CGRP induced by 10 microM anandamide was also significantly increased 6 h after LPS administration. The relaxant responses induced by anandamide in mesenteric beds isolated from either untreated or LPS-treated rats were abolished after a 2 h exposure to 10 microM capsaicin. Moreover, anandamide-induced relaxations of untreated mesenteries were potentiated by the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA, 0.1 microM), but not by its inactive analogue 4alpha-phorbol (0.1 microM). The potentiation of anandamide effects caused by the PKC activator was accompanied by a significant increase in the overflow of CGRP induced by anandamide in the untreated rats. It is proposed that the overexpression of the TRPV1 receptors and the increased content of CGRP could contribute to the enhancement of anandamide effects during the endotoxemic shock. An eventual phosphorylation event linked to the overflow of CGRP could also participate in the enhanced relaxation caused by anandamide in endotoxemia.
    MeSH term(s) Animals ; Arachidonic Acids/pharmacology ; Calcitonin Gene-Related Peptide/biosynthesis ; Endocannabinoids ; Endotoxemia/etiology ; Endotoxemia/metabolism ; Lipopolysaccharides ; Male ; Mesentery/drug effects ; Mesentery/physiology ; Norepinephrine/pharmacology ; Phorbols/pharmacology ; Polyunsaturated Alkamides/pharmacology ; Protein Kinase C/metabolism ; Rats ; Rats, Sprague-Dawley ; TRPV Cation Channels/biosynthesis ; Tetradecanoylphorbol Acetate/pharmacology ; Tongue/metabolism ; Vasoconstrictor Agents/pharmacology ; Vasodilation/drug effects
    Chemical Substances Arachidonic Acids ; Endocannabinoids ; Lipopolysaccharides ; Phorbols ; Polyunsaturated Alkamides ; TRPV Cation Channels ; Trpv1 protein, rat ; Vasoconstrictor Agents ; Calcitonin Gene-Related Peptide (83652-28-2) ; Protein Kinase C (EC 2.7.11.13) ; Tetradecanoylphorbol Acetate (NI40JAQ945) ; anandamide (UR5G69TJKH) ; Norepinephrine (X4W3ENH1CV) ; phorbol (XUZ76S9127)
    Language English
    Publishing date 2007-07-02
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80121-5
    ISSN 1879-0712 ; 0014-2999
    ISSN (online) 1879-0712
    ISSN 0014-2999
    DOI 10.1016/j.ejphar.2007.03.032
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 522: Show issues Location:
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