Participação de canais de potássio no mecanismo de ação tocolítico da 2 - (3,4 - dihidroxifenil) - 3 fenil2 - 3, dihidroquinazolin 4(1H) - ona em útero isolado de rata

Abstract

Uterine contractile activity plays an important role in many and varied reproductive functions, including sperm and embryo transport, nidation, menstruation, gestation and childbirth. An abnormal contractility of the uterine myometrium may underlie common and important disorders such as infertility, failure of nidation, dysmenorrhea, endometriosis, miscarriage or premature delivery. RETRO-2 and RETRO-5 are dihydroquinazolinones obtained by organic synthesis, which share a common nucleus. This study aimed to investigate a possible tocolytic effect of these two dihydroquinazolinones in the uterus of virgin rats. For both segments of rat uterus were suspended in tub for isolated organs and isometric contractions were monitored. RETRO-2 was not able to significantly relax the uterine strips. RETRO-5, however, significantly relaxed and concentration-dependent (EC50 = 2.4 ± 0.6 x 10-5 M) when the uterus was pre-contracted by oxytocin. However, when pre-contracted by 60 mM KCl, it had its attenuated potency (EC50 = 1.1 ± 0.1 x 10-4 M), suggesting a positive channel modulation for potassium. In the presence of TEA + 10 mM, non-selective K+ channel blocker, the tocolytic effect promoted by RETRO-5 was attenuated (EC50 = 1.5 ± 0.6 x 10-4 M), confirming the participation of these channels in its mechanism. In the presence of selective blockers such as TEA + 1mM (BKCa blocker), BaCl2 (Kir blocker) and 4-AP (KV blocker), the relaxing potency of RETRO-5 was not altered, discarding the participation of these channels. On the other hand, in the presence of glibenclamide (KATP blocker) the relaxing potency was attenuated (EC50 = 1.6 ± 0.2 x 10-4 M) and in the presence of apamine (SKCa blocker) had its relaxation practically abolished, Emax = 18.4% ± 4%, thus suggesting that these potassium channels are involved in the tocolytic mechanism of this substance. Given the data presented, we can suggest that, at least in part and at the functional level, the mechanism of action by which RETRO-5 exerts its tocolytic effect in rat uterus involves the positive modulation of KATP and SKCa.