AJP - Gastrointestinal and Liver Physiology, Vol 271, Issue 2 370-G376, Copyright © 1996 by American Physiological Society

ARTICLES

Nongenomic effects of progesterone on human intestinal smooth muscle cells

K. Bielefeldt, L. Waite, F. M. Abboud and J. L. Conklin
Department of Internal Medicine, University of Iowa, Iowa City 52242, USA.

Previous experiments demonstrated that progesterone affects intestinal smooth muscle cells through genomic and nongenomic pathways. We hypothesized that the nongenomic effect was mediated by changes in membrane excitability. We studied the effects of progesterone and other steroid hormones on a human intestinal smooth muscle cell line, using the whole cell patch-clamp technique. Ionic currents were elicited through steps from -70 mV to various test potentials. Progesterone dose-dependently reduced calcium currents. The decrease in inward current was partly due to a shift in the steady-state inactivation to more hyperpolarized potentials. This effect did not involve gene transcription, since it was not blocked by the progesterone antagonist ZK-98-299. The progesterone analogue 5-beta-dihydroprogesterone also decreased calcium currents, whereas its stereoisomer, 5-alpha- dihydroprogesterone, did not affect the properties of voltage-sensitive ion channels. Similarly, estradiol and dexamethasone did not alter inward currents. We conclude that progestins exert their nongenomic effects on intestinal smooth muscle cells by decreasing calcium currents. The change in the calcium signal may contribute to the reduction in muscle contraction observed after progesterone.

This article has been cited by other articles:

				Z.-L. Xiao, W. Cao, P. Biancani, and J. Behar Nongenomic effects of progesterone on the contraction of muscle cells from the guinea pig colon Am J Physiol Gastrointest Liver Physiol, May 1, 2006; 290(5): 1008 - 1015. [Abstract] [Full Text] [PDF]

				R. M. LOSEL, E. FALKENSTEIN, M. FEURING, A. SCHULTZ, H.-C. TILLMANN, K. ROSSOL-HASEROTH, and M. WEHLING Nongenomic Steroid Action: Controversies, Questions, and Answers Physiol Rev, July 1, 2003; 83(3): 965 - 1016. [Abstract] [Full Text] [PDF]

				Y. Zhu, J. Bond, and P. Thomas Identification, classification, and partial characterization of genes in humans and other vertebrates homologous to a fish membrane progestin receptor PNAS, March 4, 2003; 100(5): 2237 - 2242. [Abstract] [Full Text] [PDF]

				R. D. Minshall, D. Pavcnik, D. L. Browne, and K. Hermsmeyer Nongenomic vasodilator action of progesterone on primate coronary arteries J Appl Physiol, February 1, 2002; 92(2): 701 - 708. [Abstract] [Full Text] [PDF]

				A. D. Shcherbatko, C. M. Davenport, J. C. Speh, S. R. Levinson, G. Mandel, and P. Brehm Progesterone treatment abolishes exogenously expressed ionic currents in Xenopus oocytes Am J Physiol Cell Physiol, March 1, 2001; 280(3): C677 - C688. [Abstract] [Full Text] [PDF]

				N. Aytug, A. Giral, N. Imeryuz, F. Y. Enc, N. Bekiroglu, G. Aktas, and N. B. Ulusoy Gender influence on jejunal migrating motor complex Am J Physiol Gastrointest Liver Physiol, February 1, 2001; 280(2): G255 - G263. [Abstract] [Full Text] [PDF]

				E. Falkenstein, H.-C. Tillmann, M. Christ, M. Feuring, and M. Wehling Multiple Actions of Steroid Hormones---A Focus on Rapid, Nongenomic Effects Pharmacol. Rev., December 1, 2000; 52(4): 513 - 556. [Abstract] [Full Text] [PDF]

				G. R. Ehring, H. H. Kerschbaum, C. Eder, A. L. Neben, C. M. Fanger, R. M. Khoury, P. A. Negulescu, and M. D. Cahalan A Nongenomic Mechanism for Progesterone-mediated Immunosuppression: Inhibition of K+ Channels, Ca2+ Signaling, and Gene Expression in T Lymphocytes J. Exp. Med., November 2, 1998; 188(9): 1593 - 1602. [Abstract] [Full Text] [PDF]

				R. D. Minshall, K. Miyagawa, C. C. Chadwick, M. J. Novy, and K. Hermsmeyer In vitro modulation of primate coronary vascular muscle cell reactivity by ovarian steroid hormones FASEB J, October 1, 1998; 12(13): 1419 - 1429. [Abstract] [Full Text]