The relaxant action of BRL 34915 in rat uterus

Abstract

1 BRL 34915 (0.04-1.3 μm) caused concentration-dependent inhibition of spontaneous phasic spasms of the isolated uterus of the term pregnant rat and this effect was not antagonized by propranolol. Spasms evoked by low concentrations of KCl (< 20 mm) were inhibited by BRL 34915 but those evoked by higher concentrations (> 40 mm) were unaffected. 2 In experiments using extracellular electrical recording, BRL 34915 (10 μm) selectively inhibited oxytocin-induced phasic spasms and the associated spike activity but had little effect on the tonic component of the spasms. BRL 34915, as an inhibitor of phasic spasms to oxytocin (0.2 nm), was antagonized by procaine (0.3 and 1 mm). 3 BRL 34915 (10 μm) did not inhibit Ca²⁺-induced spasm of saponin-skinned thin myometrial strips. 4 Intracellular microelectrode recording from myometrial strips showed that BRL 34915 (10 μm) inhibited action potentials and phasic spasms in the presence of oxytocin (0.2 nm) and produced a hyperpolarization of 5 mV. 5 In single myometrial cells under current or voltage clamp, BRL 34915 (10 μm) had no effect on action potentials and inward current in Ca²⁺- or Ba²⁺-containing media in the presence of tetraethylammonium, 4-aminopyridine and caesium chloride. In the absence of these K⁺-channel inhibitors, BRL 34915 had no effect on resting membrane potential, membrane resistance, action potentials, inward current or outward current. 6 BRL 34915 (1 or 10 μm) had no effect on ⁸⁶Rb efflux from myometrial strips. ⁸⁶Rb efflux was increased by oxytocin (0.2 and 20 nm). 7 The relaxant profile of BRL 34915 in the rat uterus is similar to that described for other smooth muscles where an action to open membrane K⁺-channels has been proposed. BRL 34915 inhibited spike production but produced only a small hyperpolarization without a detectable increase in ⁸⁶Rb efflux. Membrane resistance and transmembrane currents were unaffected. These results suggest that in the uterus the effects of BRL 34915 may be restricted to K⁺-channels involved in the production of pacemaker activity.