The aim of this study was to compare the effect of two known spasmogens, oxytocin and the stable thromboxane receptor mimetic, U46619, on human myometrium treated with the prostaglandin E receptor (EP2) agonist, butaprost (selective for the EP2 receptor). Strips of myometrium from pregnant and non-pregnant donors were set up in a superfusion apparatus. Butaprost was administered as a bolus dose and via infusion. During the infusion of 10(-6) M butaprost, spasmogens were administered as bolus doses. Butaprost caused dose-related inhibition of myometrial activity when administered as a bolus dose (3-100 nmol) and concentration-dependent inhibition during infusion studies (10(-8)-10(-5 )M). Butaprost (10(-6 )M) attenuated the response to U46619 (0.l-10 nmol) in pregnant myometrium, but this difference was not statistically significant. Responses of pregnant myometrium to oxytocin (0.01-0.1 nmol) were significantly attenuated (P<0.05) in the presence of butaprost (10(-6)M). Butaprost physiologically antagonised the oxytocin response, possibly by increasing intracellular cAMP levels. This antagonism was much more marked than that seen with butaprost and U46619. It is unclear why these two types of antagonism differ and this effect is currently being investigated further using other prostanoid and non-prostanoid agents.
N Duckworth, K Marshall and JK Clayton
F Abbas, JK Clayton, KM Marshall and J Senior
The aim of this study was to determine the kinin responses on human umbilical artery (HUA) and to characterise the kinin receptors present on this tissue. The HUA was found to constrict in response to both the B2 receptor agonist, bradykinin (BK), and the B1 receptor agonist, des-Arg9-BK. The presence of indomethacin (2.79 microM) was found to have no significant effect on the responses to BK and des-Arg9-BK. The presence of the B2 receptor antagonist, HOE-140 (+2.79 microM indomethacin), resulted in a concentration-related rightward displacement of the concentration-effect curves to BK. The antagonism of the constrictor responses to BK by HOE-140 was found to be competitive (pA2 = 7.5). The responses to BK were not significantly affected by the B1 receptor antagonist des-Arg9(leu8)BK. The presence of des-Arg9(leu8)BK (+2.79 microM indomethacin) resulted in a concentration-related rightward displacement of the concentration-effect curve to des-Arg9-BK. The antagonism of the response to des-Arg9-BK by des-Arg9(leu8)BK was found to be competitive (pA2 = 5.9). The responses to des-Arg9-BK were not significantly affected by HOE-140. The results of the present study suggest that the products of the cyclooxygenase pathway are not involved in the kinin constrictor response on HUA and indicate the presence of B1 and B2 receptors on this tissue.