A bibliographic database and information retrieval system in prosthetics and orthotics
Jones, D.; Smart, H.; Hughes, J.
Health Bulletin 49(4): 277-284
1991
ISSN/ISBN: 0374-8014 PMID: 1938386 Document Number: 378031
A previous report from this laboratory showed that two DDT isomers, o,p'-DDT and p,p'-DDD, increased the frequency of spontaneous oscillatory contractions to a similar extent in isolated rat uterine segments. Because regulation of intracellular calcium is fundamental for the development of oscillatory contractions, the present study examined the effects of p,p'-DDD on intracellular free calcium concentration ((Ca-2+)-i) in individual rat myometrial smooth muscle cells loaded with the fluorescent Ca-2+ indicator fura 2. In the presence of extracellular calcium, 50 and 100 mu-M p,p'-DDD significantly increased peak (Ca-2+)-i 586 and 921%, respectively, over basal (Ca-2+)-i. No significant effect was observed with 10 mu-M p,p'-DDD. In the absence of extracellular calcium, the response to 100 mu-M p,p'-DDD was significantly attenuated, with cells averaging a 108% increase in peak (Ca-2+)-i over basal levels, presumably through Ca-2+ release from intracellular stores. Nifedipine and cadmium chloride, blockers of voltage-dependent calcium channels, inhibited 100 mu-M p,p'-DDD-stimulated increases in (Ca-2+)-i such that peak (Ca-2+)-i was increased 250% and 259%, respectively. Because of the prominent inhibition observed with the voltage-dependent calcium channel blockers, the effect of p,p'-DDD on membrane depolarization was examined using a cationic fluorescent indicator of membrane potential. (diS-C-2(5)). A concentration of 50 mu-M p,p'-DDD depolarized the cells by 35% of maximum during treatment with p,p'-DDD. The data demonstrate that p,p'-DDD increased (Ca-2+)-i in rat myometrial smooth muscle cells in a concentration-related manner, and that this increase was largely dependent on influx of extracellular calcium through dihydropyridine-sensitive, voltage-dependent calcium channels. The data further show that p,p'-DDD depolarized the plasma membrane, providing a possible mechanism for activation of voltage-dependent calcium channels. Additionally, another calcium source, perhaps an intracellular pool, contributes significantly less to the rise of (Ca-2+)-i Whether pp'-DDD initiates the calcium response by direct actions on the plasma membrane or by other means remains to be determined.