Apamin inhibits NO-induced relaxation of the spontaneous contractile activity of the myometrium from non-pregnant women.
There is now considerable evidence for the involvement of K+ channels in nitric oxide (NO) induced relaxation of smooth muscles including the myometrium. In order to assess whether apamin-sensitive K+ channels play a role in NO - induced relaxation of the human uterus, we have studied the effect of specific blockers of these channels on the relaxation of myometrium from non-pregnant women. In vitro isometric contractions were recorded in uterine tissues from non-pregnant premenopausal women who had undergone hysterectomy. Apamin (10 nM) and scyllatoxin (10 nM) did not alter spontaneous myometrial contractions. However, 15-min pretreatment of the myometrium strips with apamin completely inhibited relaxation caused by diethylamine-nitric oxide (DEA/NO). The pretreatment with scyllatoxin significantly reduced (about 2.6 times) maximum relaxation of the strips induced by DEA/NO (p < 0.05). These results strongly suggest that, beside Ca2+ and voltage dependent charybdotoxin-sensitive (CTX-sensitive) K+ channels, apamin-sensitive K+ channels are also present in the human non-pregnant myometrium. These channels offer an additional target in the development of new tocolytic agents.
Modzelewska
Beata
B
Department of Biophysics, Medical University of Bialystok, ul, Mickiewicza 2A, 15-089 Bialystok, Poland. beamo@amb.edu.pl
Kostrzewska
Anna
A
Sipowicz
Marek
M
Kleszczewski
Tomasz
T
Batra
Satish
S
D000328:Adult; D001030:Apamin / Q000494:pharmacology*; D018999:Charybdotoxin / Q000494:pharmacology; D005260:Female; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D017136:Ion Transport; D008875:Middle Aged; D009126:Muscle Relaxation / Q000187:drug effects; D009215:Myometrium / Q000187:drug effects*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D000644:Quaternary Ammonium Compounds / Q000037:antagonists & inhibitors; D012604:Scorpion Venoms / Q000494:pharmacology; D014590:Uterine Contraction / Q000187:drug effects*
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D000644:Quaternary Ammonium Compounds; D012604:Scorpion Venoms; C033799:apamin receptor; C087375:charybdotoxin receptor; C406802:diethylammonium-1-(N,N-diethylamino)diazen-1-ium-1,2-diolate; D018999:Charybdotoxin; C056574:leiurotoxin I; D001030:Apamin; D009569:Nitric Oxide; D011188:Potassium