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NO‐induced relaxation of labouring and non‐labouring human myometrium is not mediated by cyclic GMP
Author(s) -
Buxton Iain L O,
Kaiser Robert A,
Malmquist Nicholas A,
Tichenor Stephen
Publication year - 2001
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704226
Subject(s) - myometrium , iberiotoxin , charybdotoxin , endocrinology , medicine , chemistry , oxytocin , nitric oxide , muscle relaxation , uterus , potassium channel
In myometrial strips from near‐term non‐labouring human uterus, addition of oxytocin (OT) evoked dose‐dependent (10 – 3000 n M ) phasic contractions that were antagonized by atosiban (1 μ M ) and relaxed by addition of the nitric oxide donor S‐nitroso L‐cysteine (Cys‐NO). In near‐term labouring myometrium, however, addition of OT was ineffective at raising additional tone. In both labouring and non‐labouring tissue, Cys‐NO mediated relaxation of spontaneous or OT‐induced contractions (IC 50 =1 μ M ) was unaffected by prior addition of the guanylyl cyclase (GC) inhibitors ODQ (1H‐[1,2,4]oxadiazolo[4,3,‐α]quinoxalin‐1‐one; 1 μ M ), or methylene blue (MB; 10 μ M ). Elevation of intracellular cyclic GMP accompanying 30 μ M Cys‐NO addition in non‐labouring tissue (7.5 fold) or in labouring tissues (2.5 fold) was completely blocked in tissues that had been pre‐treated with ODQ or MB. Charybdotoxin (ChTx), iberiotoxin (IbTx) and kaliotoxin (KalTx) all shifted the Cys‐NO inhibition curve to the right and reduced the degree of relaxation produced by maximal Cys‐NO treatment (100 μ M in non‐labouring tissue; in labouring tissue, KalTx prevented Cys‐NO mediated relaxation in both stimulated and unstimulated tissue. Addition of the NO‐donor S‐nitroso N‐acetyl penicillamine (SNAP) produced a dose‐dependent relaxation of pregnant myometrium while 3‐morpholinosyndonimine (SIN‐1) did not. The failure of SIN‐1 to relax OT‐induced contractions was not due to a failure of the donor to stimulate myometrial GC. We demonstrate that despite the ability of NO to stimulate myometrial GC in pregnant uterine muscle, relaxations are independent of cyclic GMP action. Effects of K + ‐channel inhibitors suggests that NO‐induced relaxation in human uterine smooth muscle may be subserved by direct or indirect activation of one or more calcium‐activated K + ‐channels.British Journal of Pharmacology (2001) 134 , 206–214; doi: 10.1038/sj.bjp.0704226