Non-genomic effects of progesterone on human intestinal smooth
muscle cells.
Bielefeldt, Klaus, Laurie Waite, Francois M. Abboud, and Jeffrey L.
Conklin.
University of Iowa, Department of Internal Medicine
APStracts 3:0054G, 1996.
Previous experiments demonstrated that progesterone affects intestinal
smooth muscle cells through genomic and non-genomic pathways. We
hypothesized that the non-genomic 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 as it was not blocked by the progesterone
antagonist ZK 98 299. The progesterone analogue 5-
-dihydroprogesterone also decreased calcium currents, while its
stereoisomer 5--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 non-genomic 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.
Received 12 April 1995; accepted in final form 21 February 1996.
APS Manuscript Number G154-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 21 March 96