Variable responses to prostaglandin E-2 in human non-pregnant myometrium

Cumulative concentration-effect curves for prostaglandin E-2 sulprostone an d butaprost were constructed in matched strips of human non-pregnant myomet rium from 14 different donors. All samples were obtained from the mid-later al wall of the uterus. Prostaglandin E, produced four types of concentratio n-effect curves: monophasic inhibitory (n = 7), monophasic excitatory (n = 2), biphasic consisting of an excitatory phase followed by an inhibitory ph ase (n = 4), and biphasic consisting of an inhibitory phase followed by an excitatory phase (n = 1). Sulprostone produced excitation of spontaneous co ntractile activity in all tissues (mean pEC(50) = 9.1 +/- 0.2, range 8.1-10 .1, n = 14). Butaprost produced relaxation of cloprostenol-stimulated contr actile activity in all tissues (mean pEC(50) = 5.7 +/- 0.1, range 5.0-6.9, n= 14). The mean pEC(50) value for sulprostone was significantly higher in tissues when prostaglandin E-2 caused some excitation (pEC(50) = 9.4 +/- 0. 2, n = 7) compared to those where prostaglandin E, caused only inhibition ( pEC(50) = 8.8 +/- 0.2, n = 7). Mean pEC(50) values for butaprost were not s ignificantly different between these groups. These data suggest that (a) va riability in EP receptor-mediated responses exists within a single anatomic al site; (b) both excitatory and inhibitory EP receptor-mediated pathways a re always operative in human non-pregnant myometrium, regardless of the typ e of tissue response to prostaglandin E-2; and (c) regulation of EP recepto r-mediated responses occurs predominantly in the excitatory (EP, or EP, rec eptor) pathway rather than the inhibitory (EP, receptor) pathway. (C) 2001 Elsevier Science B.V. All rights reserved.