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 Ca(2+ )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.