Mechanisms underlying the neurokinin A-induced contraction of the pregnantrat myometrium

1 Using fura-PE3 fluorimetry and cc-toxin permeabilization, the characteris tics of the contractile responses to neurokinin A (NKA) were determined in the pregnant rat myometrium. 2 NKA induced contractions in rat myometrium in a concentration-dependent m anner. There were no significant differences in the maximum contractions an d EC50 values between the pregnant and non-pregnant myometrium, however, th e contraction of only the former was greatly enhanced in the presence of ph osphoramidon (PPAD), an endopeptidase inhibitor. 3 In the pregnant myometrium, NKA induced sustained increases in [Ca2+](i) and tension in normal physiological saline solution, while only small trans ient increases in [Ca2+](i) and tension were observed in Ca2+-free solution . 4 Both diltiazem (10 mu M) and SK-F 96365 (10 mu M) significantly inhibited the NKA-induced elevations of [Ca2+](i) and tension. The effects were addi tive when these drugs were used together. 5 NKA induced a significant leftward shift of the [Ca2+](i)-tension curve o btained by changing the external Ca2+ (0-2.5 mM) during depolarization with high K+ solution. This Ca2+-sensitizing effect by NKA was also observed in the alpha-toxin permeabilized myometrium. 6 These results indicated that in the pregnant rat myometrium: (1) the resp onsiveness to NKA increased, although it was masked by the increase in the endopeptidase activity; (2) NKA induced contractions of the myometrium by i ncreasing both [Ca2+](i) and the myofilament Ca2+ sensitivity and (3) The N KA-induced [Ca2+](i) elevation was partly due to the intracellular Ca2+ rel ease and mainly due to the Ca2+ influx, which was thought to be through bot h voltage dependent calcium channels and non-specification channels.