Nongenomic effects of progesterone on the contraction of muscle cells from the guinea pig colon.
Progesterone (PG) affects muscle cells by genomic mechanisms through nuclear receptors and by nongenomic mechanisms through unidentified pathways. This study aimed to determine the pathways mediating its nongenomic actions. Experiments were performed in dissociated muscle cells from guinea pig colons. Nongenomic 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 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 extracellular calcium. PG also blocked the contraction induced by inositol 1,4,5-trisphosphate, thapsigargin, and caffeine, agents that contract muscle cells by releasing calcium from storage sites. The nongenomic actions of PG were transient because they were absent 1 h after the first PG dose, remaining unresponsive after a second PG dose was administered. Furthermore, PG had no effect on the contraction induced by CCK-8 and thapsigargin in muscle cells from animals pretreated with daily intramuscular PG for 4 days. Cytosolic incorporation experiments of [(3)H]PG showed that pretreatment with unlabeled PG significantly reduced the radiolabeled PG incorporation in the cytosol. We conclude that the nongenomic actions of PG on colonic muscle cells transiently blocked calcium release from storage sites, and this response became rapidly desensitized. This effect does not appear to be specific to PG because other steroid hormones such as aldosterone and testosterone can also induce it.
Xiao
Zuo-Liang
ZL
Division of Gastroenterology, APC 406, Rhode Island Hospital/Brown University Medical School, 593 Eddy St., Providence, RI 02903, USA. zuoliangxiao2000@yahoo.com
Cao
Weibiao
W
Biancani
Piero
P
Behar
Jose
J
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003106:Colon / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D006168:Guinea Pigs; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D015288:Neurokinin A / Q000031:analogs & derivatives / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology*; D019284:Thapsigargin / Q000494:pharmacology; D013997:Time Factors
D010446:Peptide Fragments; C079306:neurokinin A (4-10)-OH; D011374:Progesterone; D019284:Thapsigargin; D015288:Neurokinin A; D002118:Calcium