Submitted on August 17, 2005
Accepted on December 19, 2005
Non-Genomic Effects of Progesterone on the Contraction of Muscle Cells from Guinea Pig Colon
Zuo-Liang Xiao1*, Weibiao Cao1, Piero Biancani1, and Jose Behar1
1 Department of Medicine, Rhode Island Hospital and Brown University School of Medicine, Providence, RI 02903, USA
* To whom correspondence should be addressed. E-mail: zuoliangxiao2000{at}yahoo.com.
Progesterone (PG) affects muscle cells by genomic mechanisms through nuclear receptors and by non-genomic mechanisms through unidentified pathways. These studies were aimed at determining the pathways mediating its non-genomic actions. Experiments were performed in dissociated muscle cells from guinea pig colons. Non-genomic actions were defined as those occurring within 10 min of PG exposure. PG blocked the contraction to CCK-8 and NKA (10-7 M) but it did not impair ACh (10-7 M) and KCl (2.5 x 10-2 M) induced contraction. Both CCK-8 and NKA contract muscle cells by releasing calcium from intracellular stores, whereas ACh and KCl can utilize extra-cellular calcium. PG also blocked the contraction induced by IP3, thapsigargin and caffeine, agents that contract muscle cells by releasing calcium from storage sites. The non-genomic actions of PG were transient since they were absent 1 h after the first PG dose, remaining unresponsive after a second PG dose was administered. Further, PG had no effect on the contraction induced by CCK-8 and thapsigargin in muscle cells from animals pre-treated with daily IM PG for four days. Cytosolic incorporation studies of 3H-PG showed that pretreatment with unlabeled PG significantly reduced the radio labeled PG incorporation in the cytosol. We conclude that the non-genomic actions of PG on colonic muscle cells transiently blocked calcium release from storage sites, and this response becomes rapidly desensitized. This effect does not appear to be specific to PG since other steroid hormones such as aldosterone and testosterone can also induce it.
