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

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 A 2 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.