PAR-2 activating peptide-induced stimulation of pregnant rat myometrium contractile activity partly involves the other membrane receptors

Nele Freerksen, Ancizar Betancourt, Holger Maul, Melissa Wentz, Phyllis Orise, Hans Heinrich Günter, Christof Sohn, Yuri Vedernikov, George Saade, Robert Garfield

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Objective: To study if spontaneous contractions augmented by proteinase-activated receptor-2 (PAR-2)-activating peptide serine-leucine-isoleucine-glycine-arginine-leucine (SLIGRL) involve coactivation of membrane chemoceptors and are associated with expression of PAR-2 mRNA in non-pregnant and pregnant rat myometrium. Materials and methods: Non-pregnant, mid-pregnant, and late pregnant rat uterine horn and small intestine segments were snap-frozen in liquid nitrogen to determine PAR-2 mRNA levels by real time polymerase chain reaction (PCR). Uterine rings were used for isometric tension recording. Effect of SLIGRL (0.1 mM) on spontaneous contractions before and after exposure to ibuprofen (cyclooxygenase inhibitor, 1.0 μM), SQ-29548 (thromboxane A2 receptor inhibitor, 1.0 μM), ketotifen (histamine 1 receptor inhibitor, 10 μM), WEB-2170BS (platelet-activating factor (PAF) receptor inhibitor, 10 μM), atropine (muscarinic receptor inhibitor, 0.1 μM), or ketanserin (serotonin receptor inhibitor, 10 μM) were compared. Paired t-test and one-way ANOVA followed by Dunnett's or Newman-Keuls post hoc tests were used for statistical analysis when appropriate. Significance: P < 0.05. Results: The agents did not significantly affect time-associated decay in spontaneous contractile activity in any group of the tissues. Activation of spontaneous contractions induced by SLIGRL in non-pregnant rat myometrium did not involve coactivation of membrane chemoceptors, while in mid-pregnant rat myometrium coactivation of prostanoid, histamine, and serotonin receptors and in late pregnant rat myometrium coactivation of thromboxane receptors was noted. Expression of PAR-2 mRNA was similar in non-pregnant, mid-pregnant, and late pregnant rat myometrium. Conclusions: Expression of PAR-2 in rat myometrium is not dependent on gestational age. Stimulation of PAR-2 is associated with production/release of cyclooxygenase pathway product(s) activating thromboxane/prostaglandin H2 receptors, partial involvement of histamine H1 receptors and serotonin receptors in midpregnancy and thromboxane A2/prostaglandin H2 receptors in late pregnancy.

Original languageEnglish (US)
Pages (from-to)51-59
Number of pages9
JournalEuropean Journal of Obstetrics Gynecology and Reproductive Biology
Volume130
Issue number1
DOIs
StatePublished - Jan 2007

Fingerprint

PAR-2 Receptor
Myometrium
Leucine
Peptides
Prostaglandin H2 Receptors Thromboxane A2
Membranes
Isoleucine
Serotonin Receptors
Glycine
Serine
Arginine
Histamine Receptors
Messenger RNA
Thromboxane Receptors
Ketotifen
Histamine H1 Receptors
Ketanserin
Cyclooxygenase Inhibitors
Ibuprofen
Thromboxanes

Keywords

  • Membrane chemoceptors
  • Myometrium
  • Proteinase-activated receptor 2
  • Proteinase-activated receptor 2-activating peptide SLIGRL
  • Uterine contractility

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Reproductive Medicine

Cite this

PAR-2 activating peptide-induced stimulation of pregnant rat myometrium contractile activity partly involves the other membrane receptors. / Freerksen, Nele; Betancourt, Ancizar; Maul, Holger; Wentz, Melissa; Orise, Phyllis; Günter, Hans Heinrich; Sohn, Christof; Vedernikov, Yuri; Saade, George; Garfield, Robert.

In: European Journal of Obstetrics Gynecology and Reproductive Biology, Vol. 130, No. 1, 01.2007, p. 51-59.

Research output: Contribution to journalArticle

Freerksen, Nele ; Betancourt, Ancizar ; Maul, Holger ; Wentz, Melissa ; Orise, Phyllis ; Günter, Hans Heinrich ; Sohn, Christof ; Vedernikov, Yuri ; Saade, George ; Garfield, Robert. / PAR-2 activating peptide-induced stimulation of pregnant rat myometrium contractile activity partly involves the other membrane receptors. In: European Journal of Obstetrics Gynecology and Reproductive Biology. 2007 ; Vol. 130, No. 1. pp. 51-59.
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abstract = "Objective: To study if spontaneous contractions augmented by proteinase-activated receptor-2 (PAR-2)-activating peptide serine-leucine-isoleucine-glycine-arginine-leucine (SLIGRL) involve coactivation of membrane chemoceptors and are associated with expression of PAR-2 mRNA in non-pregnant and pregnant rat myometrium. Materials and methods: Non-pregnant, mid-pregnant, and late pregnant rat uterine horn and small intestine segments were snap-frozen in liquid nitrogen to determine PAR-2 mRNA levels by real time polymerase chain reaction (PCR). Uterine rings were used for isometric tension recording. Effect of SLIGRL (0.1 mM) on spontaneous contractions before and after exposure to ibuprofen (cyclooxygenase inhibitor, 1.0 μM), SQ-29548 (thromboxane A2 receptor inhibitor, 1.0 μM), ketotifen (histamine 1 receptor inhibitor, 10 μM), WEB-2170BS (platelet-activating factor (PAF) receptor inhibitor, 10 μM), atropine (muscarinic receptor inhibitor, 0.1 μM), or ketanserin (serotonin receptor inhibitor, 10 μM) were compared. Paired t-test and one-way ANOVA followed by Dunnett's or Newman-Keuls post hoc tests were used for statistical analysis when appropriate. Significance: P < 0.05. Results: The agents did not significantly affect time-associated decay in spontaneous contractile activity in any group of the tissues. Activation of spontaneous contractions induced by SLIGRL in non-pregnant rat myometrium did not involve coactivation of membrane chemoceptors, while in mid-pregnant rat myometrium coactivation of prostanoid, histamine, and serotonin receptors and in late pregnant rat myometrium coactivation of thromboxane receptors was noted. Expression of PAR-2 mRNA was similar in non-pregnant, mid-pregnant, and late pregnant rat myometrium. Conclusions: Expression of PAR-2 in rat myometrium is not dependent on gestational age. Stimulation of PAR-2 is associated with production/release of cyclooxygenase pathway product(s) activating thromboxane/prostaglandin H2 receptors, partial involvement of histamine H1 receptors and serotonin receptors in midpregnancy and thromboxane A2/prostaglandin H2 receptors in late pregnancy.",
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author = "Nele Freerksen and Ancizar Betancourt and Holger Maul and Melissa Wentz and Phyllis Orise and G{\"u}nter, {Hans Heinrich} and Christof Sohn and Yuri Vedernikov and George Saade and Robert Garfield",
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T1 - PAR-2 activating peptide-induced stimulation of pregnant rat myometrium contractile activity partly involves the other membrane receptors

AU - Freerksen, Nele

AU - Betancourt, Ancizar

AU - Maul, Holger

AU - Wentz, Melissa

AU - Orise, Phyllis

AU - Günter, Hans Heinrich

AU - Sohn, Christof

AU - Vedernikov, Yuri

AU - Saade, George

AU - Garfield, Robert

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N2 - Objective: To study if spontaneous contractions augmented by proteinase-activated receptor-2 (PAR-2)-activating peptide serine-leucine-isoleucine-glycine-arginine-leucine (SLIGRL) involve coactivation of membrane chemoceptors and are associated with expression of PAR-2 mRNA in non-pregnant and pregnant rat myometrium. Materials and methods: Non-pregnant, mid-pregnant, and late pregnant rat uterine horn and small intestine segments were snap-frozen in liquid nitrogen to determine PAR-2 mRNA levels by real time polymerase chain reaction (PCR). Uterine rings were used for isometric tension recording. Effect of SLIGRL (0.1 mM) on spontaneous contractions before and after exposure to ibuprofen (cyclooxygenase inhibitor, 1.0 μM), SQ-29548 (thromboxane A2 receptor inhibitor, 1.0 μM), ketotifen (histamine 1 receptor inhibitor, 10 μM), WEB-2170BS (platelet-activating factor (PAF) receptor inhibitor, 10 μM), atropine (muscarinic receptor inhibitor, 0.1 μM), or ketanserin (serotonin receptor inhibitor, 10 μM) were compared. Paired t-test and one-way ANOVA followed by Dunnett's or Newman-Keuls post hoc tests were used for statistical analysis when appropriate. Significance: P < 0.05. Results: The agents did not significantly affect time-associated decay in spontaneous contractile activity in any group of the tissues. Activation of spontaneous contractions induced by SLIGRL in non-pregnant rat myometrium did not involve coactivation of membrane chemoceptors, while in mid-pregnant rat myometrium coactivation of prostanoid, histamine, and serotonin receptors and in late pregnant rat myometrium coactivation of thromboxane receptors was noted. Expression of PAR-2 mRNA was similar in non-pregnant, mid-pregnant, and late pregnant rat myometrium. Conclusions: Expression of PAR-2 in rat myometrium is not dependent on gestational age. Stimulation of PAR-2 is associated with production/release of cyclooxygenase pathway product(s) activating thromboxane/prostaglandin H2 receptors, partial involvement of histamine H1 receptors and serotonin receptors in midpregnancy and thromboxane A2/prostaglandin H2 receptors in late pregnancy.

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KW - Uterine contractility

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