Utero‐relaxant effect of PDE4‐selective inhibitor alone and in simultaneous administration with β2‐mimetic on oxytocin‐induced contractions in pregnant myometrium

Fraňová, Soňa; Janicek, Frantisek; Višňovský, Jozef; Dokus, Karol; Žúbor, Pavol; Šutovská, Martina; Nosálóvá, G

doi:10.1111/j.1447-0756.2008.00839.x

Cited by 14 publications

(16 citation statements)

References 21 publications

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“…PDE inhibitors have been developed for treatment of inflammatory diseases, such as chronic obstructive pulmonary disease, asthma, inflammatory bowel disease and psoriasis, as well as neurological and psychiatric disorders, such as depression, schizophrenia, Parkinson's disease and chronic heart failure (Azevedo et al, 2014;Bender and Beavo, 2006). In reproductive medicine PDE4 inhibition has been suggested as a mechanism to be used for ovulation induction and as a tocolytic drug (Franova et al, 2009;McKenna et al, 2005). During preclinical development several PDE4 inhibitors have shown effects on the reproductive system in rodents (Losco et al, 2010;Nishiyama et al, 2006;U.S.…”

Section: Introductionmentioning

confidence: 99%

Distribution and function of 3′,5′-Cyclic-AMP phosphodiesterases in the human ovary

Petersen

Kristensen

Jeppesen

et al. 2015

Molecular and Cellular Endocrinology

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Section: Introductionmentioning

confidence: 99%

Distribution and function of 3′,5′-Cyclic-AMP phosphodiesterases in the human ovary

Petersen

Kristensen

Jeppesen

et al. 2015

Molecular and Cellular Endocrinology

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“…Some experimental studies show that PDE inhibitors could represent a possible future therapeutic potential in the process of myometrial contractility modulation (8,22,23). The tocolytic effects of inhibitors of phosphodiesterases were the result of the increase of intracellular cyclic nucleotides, in the case of rolipram cAMP and cGMP in sildenaphil.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of Contraction and Relaxation in Human Term Pregnant Myometrium

Sadlonova

Dokus

Janicek³

et al. 2012

Acta Medica Martiniana

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A b s t r a c tThe study discusses the problem of role of various substances in the mechanisms of contraction and relaxation of human term pregnant myometrium in the experimental in vitro conditions. Human myometrium tissue samples were collected from term pregnant women who had to undergo Caesarean section. The effects of potassium ion channels openers and closers, phosphodiesterase inhibitors and tachykinins were measured in the reactivity of human term pregnant myometrium in the experimental in vitro conditions. Specific agonist-opener of K ATP potassium ion channels -pinacidil significantly reduced contractile activity of human term pregnant myometrial strips induced by administration of oxytocin in in vitro conditions, while the effect of specific agonist-opener of BK Ca2+ potassium ion channels -NS1619 was not significant. Glibenclamide, specific K ATP potassium ion channels antagonist-closer significantly increased contractile activity of human term pregnant myometrial strips in in vitro conditions. The contractile effect of specific antagonist-closer of BK Ca2+ potassium ion channels -tetraethylammonium was not significant. Phosphodiesterase-4 inhibitor -rolipram and phosphodiesterase-5 inhibitor -sildenaphil led to statistically significant decrease of oxytocin-induced contractile activity in human term pregnant myometrial strips in in vitro conditions. Tachykinins -neurokinin A, neurokinin B and substance P markedly stimulated the activity of the human term pregnant myometrial strips in in vitro conditions.The results showed the different effectiveness of potassium ion channels openers and closers, phosphodiesterase inhibitors as well as tachykinins in the mechanisms of contraction and relaxation of human term pregnant myometrium in in vitro conditions.

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“…Agents that increase intracellular cAMP levels, including forskolin, cAMP-phosphodiesterase (PDE) type 4 inhibitors, and 8-bromo-cAMP, dose dependently inhibit human full-term nonlaboring myometrial contractile force by up to 100% (13,64,128,142,172,218,243,248). It is probable that myometrial cAMP signaling causes MYPT1 serine phosphorylation.…”

Section: )mentioning

confidence: 99%

Role of serine-threonine phosphoprotein phosphatases in smooth muscle contractility

Butler

Paul

Europe-Finner

et al. 2013

American Journal of Physiology-Cell Physiology

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The degree of phosphorylation of myosin light chain 20 (MLC20) is a major determinant of force generation in smooth muscle. Myosin phosphatases (MPs) contain protein phosphatase (PP) 1 as catalytic subunits and are the major enzymes that dephosphorylate MLC20. MP regulatory targeting subunit 1 (MYPT1), the main regulatory subunit of MP in all smooth muscles, is a key convergence point of contractile and relaxatory pathways. Combinations of regulatory mechanisms, including isoform splicing, multiple phosphorylation sites, and scaffolding proteins, modulate MYPT1 activity with tissue and agonist specificities to affect contraction and relaxation. Other members of the PP1 family that do not target myosin, as well as PP2A and PP2B, dephosphorylate a range of proteins that affect smooth muscle contraction. This review discusses the role of phosphatases in smooth muscle contractility with a focus on MYPT1 in uterine smooth muscle. Myometrium shares characteristics of vascular and other visceral smooth muscles yet, during healthy pregnancy, undergoes hypertrophy, hyperplasia, quiescence, and labor as physiological processes. Myometrium presents an accessible model for the study of normal and pathological smooth muscle function, and a better understanding of myometrial physiology may allow the development of novel therapeutics for the many disorders of myometrial physiology from preterm labor to dysmenorrhea.

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Utero‐relaxant effect of PDE4‐selective inhibitor alone and in simultaneous administration with β2‐mimetic on oxytocin‐induced contractions in pregnant myometrium

Cited by 14 publications

References 21 publications

Distribution and function of 3′,5′-Cyclic-AMP phosphodiesterases in the human ovary

Distribution and function of 3′,5′-Cyclic-AMP phosphodiesterases in the human ovary

Mechanisms of Contraction and Relaxation in Human Term Pregnant Myometrium

Role of serine-threonine phosphoprotein phosphatases in smooth muscle contractility

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