Evidence of non-synaptic regulation of postpartum uterine contractility in the rat

Gáspár, Róbert; Márki, Árpád; Zupkó, István; Falkay, George

doi:10.1016/s0024-3205(98)00035-6

Cited by 16 publications

(10 citation statements)

References 19 publications

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“…The changes in adrenergic receptor density associated with an ongoing degeneration process in the course of pregnancy and their role in the modulation of uterine contractility is well established [1][2][3][4][5]. In most visceral organs, stimulation of sensory nerves may evoke significant alterations in smooth muscle contractile activity [6,7].…”

Section: Introductionmentioning

confidence: 99%

“…This particular local regulatory or sensory efferent function is a characteristic trait of primary afferent neurons that are specifically sensitive to 1 This work was supported by the Richter Gedeon Centennial Foundation. 2 Correspondence: George Falkay, Department of Pharmacodynamics and Biopharmacy, University of Szeged, H-6720 Szeged, Eö tvö s u. 6 [11][12][13] and express the capsaicin/vanilloid VR1 receptor [14,15].…”

Section: Introductionmentioning

confidence: 99%

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Role of Capsaicin-Sensitive Nerve Fibers in Uterine Contractility in the Rat1

Klinke¹,

Gáspár²,

Stella³

et al. 2004

Biology of Reproduction

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The possible participation of capsaicin-sensitive sensory nerves in the modulation of neurogenic contractions was studied in nonpregnant and term pregnant rat uteri. Neurogenic contractions were elicited by electric field stimulation (40 V, 1-70 Hz, 0.6 msec) in intact uteri and uteri that were previously exposed to capsaicin in vitro. In capsaicin pretreated preparations obtained both from nonpregnant and term pregnant rats, a dose-dependent increase in the amplitude of uterine contractions was detected. Prior systemic treatment of the rats with capsaicin (130 mg/kg, s.c.) abolished the effect of in vitro capsaicin administration on the amplitude of neurogenic contractions. Use of a specific antagonist of calcitonin gene-related peptide revealed that depletion of this peptide, which normally elicits uterine smooth muscle relaxation, may be responsible for the increased responsiveness of the uterus to low-frequency stimulation. Experiments on the localization of calcitonin gene-related peptide in uterine tissue specimens exposed to capsaicin revealed dose-dependent depletion of calcitonin-gene related peptide-immunoreactive nerves innervating blood vessels and the myometrium. The findings indicate that capsaicin-sensitive afferent nerves, by the release of sensory neuropeptides, significantly contribute to the modulation of uterine contractility both in nonpregnant and term pregnant rats. It is suggested that uterine sensory nerve activation may be part of a trigger mechanism leading to preterm contractions evoked by, for example, inflammation.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Role of Capsaicin-Sensitive Nerve Fibers in Uterine Contractility in the Rat1

Klinke¹,

Gáspár²,

Stella³

et al. 2004

Biology of Reproduction

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“…In previous experiments, an a-AR dominance was proved at the end of pregnancy (Zupkó et al, 1997;Gá spá r et al, 1998). The number of a 1 -ARs is known to increase sharply in the last 6 hr of pregnancy, and radioligand binding assays have shown that the number of a 1A -ARs is increased by 88% at term.…”

Section: Discussionmentioning

confidence: 94%

“…In earlier experiments, it was proved that an a-AR antagonist induced a significant decrease in uterine activity in the rat both in vitro and in vivo (Zupkó et al, 1997;Gá spá r et al, 1998). Additionally, at the end of pregnancy the a 1 /b-AR ratio of the rat uterus was found to be increased, in parallel with an increase in contractility, demonstrating a very close correlation with the density of a 1 -ARs during rat pregnancy .…”

Section: Introductionmentioning

confidence: 86%

Altered levels of mRNA expression and pharmacological reactivity of α₁‐adrenergic receptor subtypes in the late‐pregnant rat myometrium

Ducza

Gáspár

Falkay

2002

Molecular Reproduction Devel

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The adrenergic system plays a major role in the regulation of the uterine contractility during pregnancy. Our previous studies have shown the significance of the alpha1-adrenergic receptors (ARs) in the control of pregnant uterine contractility both in vitro and in vivo. Our present aim was to determine the changes in mRNA expression and pharmacological reactivity of the alpha1-ARs on days 18, 20, and 22 of pregnancy. To demonstrate the expressions of alpha1-AR subtype mRNA, we used a reverse transcription-polymerase chain reaction (RT-PCR); the pharmacological reactivity was tested by electric field stimulation (EFS). The expression of alpha1A-AR mRNA increased from day 18 to 22, while no alpha1B-AR mRNA was detectable. We found a small increase in the expression of alpha1D-AR mRNA on day 20, which was not followed by a significant change in pharmacological reactivity. The alpha1D-receptor expression and pharmacological reactivity decreased significantly up to day 22. EFS studies revealed that the alpha1A-AR antagonist 5-methylurapidil had EC50 values (1.9 x 10(-6)-6.3 x 10(-6) M) about one order of magnitude lower than those of the alpha1D-AR antagonist BMY 7378 (4 x 10(-6)-3.6 x 10(-5) M). However, the alpha1B-AR antagonist cyclazosine exerted only a slight effect on the stimulated contractions. Strong correlations were found between the alpha1A-mRNA expression and the EC50 of 5-methylurapidil (r(2) =0.9712), and between the alpha1D-AR mRNA expression and the EC50 of BMY 7378 (r(2) = 0.9937). Our findings suggest that both alpha1A- and alpha1D-ARs are involved in the regulation of the pregnant uterine contractility. The density and pharmacological reactivity indicate that the alpha(1A)-AR seems to play the major role in late-pregnant myometrial contraction.

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“…Because premature cervical dilation can contribute to preterm birth of the fetus, 23 compounds that increase cervical resistance could be beneficial in the therapy of premature complications. Although a 1 -adrenoceptor inverse agonists are known to decrease uterine contractility, 28,29 no reliable information is available concerning their action on the cervix. The effect of WB 4101 on cervical resistance was expressed as the slope difference, calculated by subtraction of the average slope (0.7867) for non-treated samples from that for treated samples.…”

Section: Discussionmentioning

confidence: 99%

EFFECT OF α₁‐ADRENOCEPTOR SUBTYPE‐SELECTIVE INVERSE AGONISTS ON NON‐PREGNANT AND LATE‐PREGNANT CERVICAL RESISTANCE IN VITRO IN THE RAT

Kolarovszki-Sipiczki

Gáspár

Ducza

et al. 2006

Clin Exp Pharma Physio

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1. The aim of the present study was to compare and elucidate the effects of alpha(1)-adrenoceptor (alpha(1)-AR) subtype-selective inverse agonists on non-pregnant and late-pregnant rat cervical tone. 2. Cervical resistance was investigated in in vitro stretching tests in the absence or presence of alpha(1)-AR subtype-selective inverse agonists (WB 4101, AH 11110A and BMY 7378; all at 10(-6) mol/L), whereas the mRNA levels and density of the alpha(1)-AR subtypes and the G-protein-activating effects of the inverse agonists were determined by reverse transcription-polymerase chain reaction, western blot and [(35)S]-GTPgammaS binding techniques, respectively. 3. The inverse agonists did not cause any change in resistance in non-pregnant and 18-day-pregnant samples. WB 4101 increased cervical resistance from Day 20, whereas AH 11110A had no effect and BMY 7378 exhibited such an action only on Day 21. Phenylephrine (10(-4) mol/L) had no effect on cervical resistance on Day 22. The mRNA levels and density of all alpha(1)-AR subtypes were increased on Day 18, but no further changes were observed after that. The [(35)S]-GTPgammaS binding studies revealed increased G-protein activation of alpha(1A)-AR and a moderate G-protein activation of alpha(1B)- and alpha(1D)-AR. The effect of WB 4101 to increase [(35)S]-GTPgammaS binding was blocked by pertussis toxin (50 ng/mL). Phenylephrine caused a slight and significant decrease in the amount of activated G-protein on Day 22. 4. The effects of inverse agonists on the alpha(1A)-AR can enhance cervical resistance in the late-pregnant rat in vitro. This action is mediated, at least in part, by a pertussis toxin-sensitive G(i)-protein. This effect of the alpha(1A)-AR inverse agonist WB 4101 may offer a new therapeutic target in the prevention of premature labour.

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Evidence of non-synaptic regulation of postpartum uterine contractility in the rat

Cited by 16 publications

References 19 publications

Role of Capsaicin-Sensitive Nerve Fibers in Uterine Contractility in the Rat1

Role of Capsaicin-Sensitive Nerve Fibers in Uterine Contractility in the Rat1

Altered levels of mRNA expression and pharmacological reactivity of α₁‐adrenergic receptor subtypes in the late‐pregnant rat myometrium

EFFECT OF α₁‐ADRENOCEPTOR SUBTYPE‐SELECTIVE INVERSE AGONISTS ON NON‐PREGNANT AND LATE‐PREGNANT CERVICAL RESISTANCE IN VITRO IN THE RAT

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Evidence of non-synaptic regulation of postpartum uterine contractility in the rat

Cited by 16 publications

References 19 publications

Role of Capsaicin-Sensitive Nerve Fibers in Uterine Contractility in the Rat1

Role of Capsaicin-Sensitive Nerve Fibers in Uterine Contractility in the Rat1

Altered levels of mRNA expression and pharmacological reactivity of α1‐adrenergic receptor subtypes in the late‐pregnant rat myometrium

EFFECT OF α1‐ADRENOCEPTOR SUBTYPE‐SELECTIVE INVERSE AGONISTS ON NON‐PREGNANT AND LATE‐PREGNANT CERVICAL RESISTANCE IN VITRO IN THE RAT

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Altered levels of mRNA expression and pharmacological reactivity of α₁‐adrenergic receptor subtypes in the late‐pregnant rat myometrium

EFFECT OF α₁‐ADRENOCEPTOR SUBTYPE‐SELECTIVE INVERSE AGONISTS ON NON‐PREGNANT AND LATE‐PREGNANT CERVICAL RESISTANCE IN VITRO IN THE RAT