Relaxant effect of proton pump inhibitors on in vitro myometrium from pregnant women.
OBJECTIVE
In this study we investigate in in vitro myometrial tissue samples of pregnant women: (a) the effects of proton pomp inhibitors (PPIs) (omeprazole, esomeprazole, pantoprazole, lansoprazole and rabeprazole) on spontaneous contractions; (b) the muscle-relaxant efficacy of the most active PPI considered (pantoprazole) in comparison with that of other known tocolytics (nifedipine, atosiban, MgSO4, isoxsuprine); (c) the effect of pantoprazole on contractions induced by calcium (Ca(++)), KCl, oxytocin and prostaglandin (PGE2); (d) the possible mediators of pantoprazole relaxant effect.


METHODS
Organ bath studies were performed on myometrial tissue samples (40×10×10 mm) from pregnant women (38-42 weeks of gestational age) undergoing elective caesarian section.


RESULTS
All the PPIs studied reduce the spontaneous contraction of the myometrial smooth muscle. Pantoprazole is the most effective and most potent inhibitor among those analyzed. Pantoprazole also reduces the contractions induced by Ca(++), KCl, oxytocin and PGE2. Neither NO, nor PGs, or the activation of Ca(++)-dependent K(+) currents mediate the muscle-relaxant effect of this PPI.


CONCLUSIONS
These data, together with the fact that PPIs almost do not present side effects, suggest that these drugs can offer new therapeutic strategies for preterm delivery. Undoubtedly, further investigations and clinical studies are necessary before adding PPIs to the list of drugs available for the treatment of preterm delivery.
Department of Obstetrics and Gynaecology, "Campus Bio Medico" University, Rome, Italy.
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Terranova
Department of Physiology and Pharmacology "V. Erspamer", Sapienza University, Rome, Italy. Electronic address: carla.petrella@uniroma1.it.
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Petrella
Department of Physiology and Pharmacology "V. Erspamer", Sapienza University, Rome, Italy.
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Improta
Institute of Cellular Biology and Neurobiology, CNR, Rome, Italy.
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Severini
Department of Obstetrics and Gynaecology, San Camillo - Forlanini Hospital, Rome, Italy.
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Signore
Department of Obstetrics and Gynaecology, San Camillo - Forlanini Hospital, Rome, Italy.
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Damiani
Department of Obstetrics and Gynaecology, "Campus Bio Medico" University, Rome, Italy.
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Plotti
Division of Gastroenterology, Department of Clinical Sciences, University of Parma, Italy.
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Scarpignato
Department of Obstetrics and Gynaecology, "Campus Bio Medico" University, Rome, Italy.
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Angioli
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000494:pharmacology*; D001030:Apamin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D064098:Esomeprazole / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D064747:Lansoprazole / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009215:Myometrium / Q000187:drug effects* / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009853:Omeprazole / Q000494:pharmacology; D010121:Oxytocin / Q000494:pharmacology; D000077402:Pantoprazole; D010455:Peptides / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011247:Pregnancy; D054328:Proton Pump Inhibitors / Q000494:pharmacology*; D064750:Rabeprazole / Q000494:pharmacology; D015149:Tocolytic Agents / Q000494:pharmacology*
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D010455:Peptides; D054328:Proton Pump Inhibitors; D015149:Tocolytic Agents; D064747:Lansoprazole; D001030:Apamin; D064750:Rabeprazole; D010121:Oxytocin; D011189:Potassium Chloride; C064719:iberiotoxin; D000077402:Pantoprazole; D015232:Dinoprostone; D009853:Omeprazole; D064098:Esomeprazole; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin
Myometrial contraction; PPIs; Preterm delivery; Tocolytic effect