Melatonin receptor signaling in pregnant and nonpregnant rat uterine myocytes as probed by large conductance Ca2+-activated K+ channel activity

The mRNAs of MT1 and MT2 melatonin receptors are present in cells from nonpregnant (NPM) and pregnant (PM) rat myometrium. To investigate the coupling of melatonin receptors to Gq- and Gi-type of heterotrimeric G proteins, we analyzed the activity of large-conductance Ca2+-activated K+ (BKCa) channe...

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Main Authors: Steffens, Frank (Author) , Zhou, Xiao-Bo (Author) , Sausbier, Ulrike (Author) , Sailer, Claudia (Author) , Motejlek, Karin (Author) , Ruth, Peter (Author) , Olcese, James (Author) , Korth, Michael (Author) , Wieland, Thomas (Author)
Format: Article (Journal)
Language:English
Published: 01 October 2003
In: Molecular endocrinology
Year: 2003, Volume: 17, Issue: 10, Pages: 2103-2115
ISSN:1944-9917
DOI:10.1210/me.2003-0047
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1210/me.2003-0047
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Author Notes:Frank Steffens, Xiao-Bo Zhou, Ulrike Sausbier, Claudia Sailer, Karin Motejlek, Peter Ruth, James Olcese, Michael Korth, Thomas Wieland

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520 |a The mRNAs of MT1 and MT2 melatonin receptors are present in cells from nonpregnant (NPM) and pregnant (PM) rat myometrium. To investigate the coupling of melatonin receptors to Gq- and Gi-type of heterotrimeric G proteins, we analyzed the activity of large-conductance Ca2+-activated K+ (BKCa) channels, the expression of which in the uterus is confined to smooth muscle cells. The melatonin receptor agonist 2-iodomelatonin induced a pertussis toxin (PTX)-insensitive increase in channel open probability that was blocked by the nonselective antagonist luzindole. The 2-iodomelatonin effect on channel open probability was suppressed by overexpression of the Gqalpha-inactivating protein RGS16 and the phospholipase C inhibitor U-73122. The activity of BKCa channels is differentially regulated by protein kinase A (PKA) in NPM and PM cells. Thus, the beta-adrenoceptor agonist isoprenaline inhibited the BKCa channel conducted whole-cell outward current (Iout) in NPM cells and enhanced Iout in PM cells. Additional application of 2-iodomelatonin antagonized the isoprenaline effect on Iout in NPM cells but enhanced Iout in PM cells. All 2-iodomelatonin effects on Iout were sensitive to PTX treatment and the PKA inhibitor H-89. We therefore conclude that melatonin activates both the PTX-insensitive Gq/phospholipase C/Ca2+ and the PTX-sensitive Gi/cAMP/PKA signaling pathway in rat myometrium. 
650 4 |a Animals 
650 4 |a Calcium 
650 4 |a Cyclic AMP 
650 4 |a Cyclic AMP-Dependent Protein Kinases 
650 4 |a Female 
650 4 |a GTP-Binding Protein alpha Subunits, Gi-Go 
650 4 |a GTP-Binding Protein alpha Subunits, Gq-G11 
650 4 |a Isoproterenol 
650 4 |a Large-Conductance Calcium-Activated Potassium Channels 
650 4 |a Melatonin 
650 4 |a Membrane Potentials 
650 4 |a Myometrium 
650 4 |a Pertussis Toxin 
650 4 |a Potassium Channels, Calcium-Activated 
650 4 |a Pregnancy 
650 4 |a Rats 
650 4 |a Rats, Wistar 
650 4 |a Receptor, Melatonin, MT1 
650 4 |a Receptor, Melatonin, MT2 
650 4 |a Signal Transduction 
650 4 |a Type C Phospholipases 
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