Mediators involved in the rat uterus contraction in calcium-free solution
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A I Fernandez1, B Cantabrana, A Hidalgo
1Departamento de Medicina, Facultad de Medicina, Oviedo, Spain.
Abstract:
1. The effect of (Na+ + K+)-ATPase inhibitor ouabain (10(-5)-3 x 10(-4) M), and the (Ca2+ + Mg2+)-ATPase inhibitors vanadate (6 x 10(-6)-6 x 10(-4) M), oxytocin (2 x 10(-9)-4 x 10(-8) M, and prostaglandin F2 alpha (PGF2 alpha, 10(-7)-6 x 10(-6) M) were assayed on rat uterus incubated in Ca-free medium. 2. Vanadate, oxytocin and PGF2 alpha, but not ouabain, induced contractions in a dose-dependent way (ED50: 7.5 +/- 0.03 x 10(-5) M; 6.5 +/- 0.064 x 10(-9) M and 3.8 +/- 0.085 x 10(-7) M). 3. Vanadate (3 x 10(-4) M) and oxytocin (OT, 10 mU/ml = 2 x 10(-8) M)-induced tonic contraction were not modified by nifedipine (10(-10)-10(-6) M), monensin (10(-5)-3 x 10(-4) M) or amiloride (10(-5)-10(-3) M). 4. The intracellular calcium release inhibitors TMB-8 (10(-6)-10(-4) M) and dantrolene (3 x 10(-6)-10(-4) M), and the prostaglandin release inhibitor indomethacin (3 x 10(-8)-6 x 10(-5) M) relaxed the vanadate and OT-induced tonic contractions. 5. The calmodulin inhibitors trifluoperazine (3 x 10(-5)-3 x 10(-4) M), bepridil (10(-8)-3 x 10(-4) M), calmidazolium (10(-7)-10(-4) M) and W-7 (10(-7)-10(-5) M) also relaxed the vanadate and OT-induced tonic contractions. 6. Our results suggest that oxytocin and vanadate-induced contractions on rat uterus in Ca-free medium could be produced by release of prostaglandins and intracellular calcium, and mediated by calmodulin.
Insights
This study investigated how (Na+ + K+)-ATPase and (Ca2+ + Mg2+)-ATPase inhibitors affect rat uterus contractions in a calcium-free environment. Oxytocin and vanadate-induced contractions involve prostaglandin release, intracellular calcium, and calmodulin.
Area of Science:
- Pharmacology
- Physiology
- Biochemistry
Background:
- Uterine contractions are regulated by complex ionic and signaling pathways.
- Understanding the mechanisms of smooth muscle contraction is crucial for reproductive health and pharmacology.
Purpose of the Study:
- To investigate the effects of specific ATPase inhibitors and agonists on rat uterus contractility in a calcium-free medium.
- To elucidate the signaling pathways, including prostaglandin and intracellular calcium release, involved in vanadate and oxytocin-induced contractions.
Main Methods:
- Assaying the effects of ouabain, vanadate, oxytocin, and prostaglandin F2 alpha on isolated rat uterus in a calcium-free medium.
- Utilizing various inhibitors, including nifedipine, monensin, amiloride, TMB-8, dantrolene, indomethacin, trifluoperazine, bepridil, calmidazolium, and W-7, to probe signaling pathways.
- Dose-response analysis and determination of ED50 values for inducing contractions.
Main Results:
- Vanadate, oxytocin, and prostaglandin F2 alpha induced dose-dependent contractions, while ouabain did not.
- Vanadate and oxytocin-induced contractions were unaffected by nifedipine, monensin, or amiloride.
- Intracellular calcium release inhibitors (TMB-8, dantrolene), prostaglandin release inhibitor (indomethacin), and calmodulin inhibitors (trifluoperazine, bepridil, calmidazolium, W-7) relaxed vanadate and oxytocin-induced contractions.
Conclusions:
- Oxytocin and vanadate-induced uterine contractions in a calcium-free medium are mediated by prostaglandin release and intracellular calcium mobilization.
- Calmodulin plays a significant role in mediating these contractions.
- These findings provide insights into the pharmacological regulation of uterine contractility.