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Am J Physiol Gastrointest Liver Physiol 297: G886-G893, 2009. First published September 17, 2009; doi:10.1152/ajpgi.00184.2009
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NEUROREGULATION AND MOTILITY

Effects of progesterone on motility and prostaglandin levels in the distal guinea pig colon

Zuo Liang Xiao,1 Piero Biancani,2 and Jose Behar2

1Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio; 2Department of Medicine, Rhode Island Hospital and the Alpert Medical School of the Brown University, Providence, Rhode Island

Submitted May 14, 2009 ; accepted in final form September 1, 2009

Progesterone (P4) inhibits the gastrointestinal muscle contraction by downregulating G{alpha}q/11 proteins that mediate contraction, by upregulating G{alpha}s proteins that mediate relaxation, and by altering the pattern of cyclooxygenase (COX) enzymes and prostaglandins. We aimed to examine whether P4 treatment of guinea pigs in vivo affects basal colon motility [basal motility index (MI)] by altering the levels and actions of PGF2{alpha} and PGE2. Guinea pigs were treated with intramuscular (IM) P4 for 4 days. The BASAL MI, the PGF2{alpha}-induced contraction, and PGE2-induced inhibition of contraction were examined in muscle strips and cells. The levels of PGF2{alpha} and PGE2 were measured by radioimmunoassay. Treatment with P4 reduced the basal MI, the levels of PGF2{alpha}, and PGF2{alpha}-induced contraction. P4 increased PGE2 levels, and PGE2 induced relaxation. Pretreatment with IM RU-486 (10 mg/kg per day), a P4 receptor antagonist, 1 h before P4 blocked the actions of P4. The PGF2{alpha} antagonist Al-1180 abolished basal MI and PGF2{alpha}-induced contraction. N-ethylmaleimide, which blocks unoccupied membrane receptors, blocked Ach and VIP actions but had no effect on PGF2{alpha} and PGE2 effects. A COX-1 inhibitor decreased and a COX-2 inhibitor increased PGF2{alpha} levels; GTP{gamma}S increased and GDPβS decreased the levels of PGF2{alpha}. G{alpha}q/11 protein antibodies (Abs) reduced PGF2{alpha} levels, and G{alpha}i3 Abs blocked its motor actions. G{alpha}s Abs increased PGF2{alpha} but decreased PGE2 levels. We concluded that P4 decreases basal MI by reducing PGF2{alpha} levels caused by downregulation of G{alpha}q/11 and that PGF2{alpha}-induced contraction was blocked by downregulating G{alpha}i3. P4 also decreased the basal MI by increasing PGE2 levels, and PGE2 induced relaxation by upregulating G{alpha}s proteins.

colon motility; guinea pigs; PGF2{alpha}; PGE2; G proteins


Address for reprint requests and other correspondence: J. Behar, Div. of Gastroenterology, APC 421, 593 Eddy St., Providence, RI 02903 (e-mail: Jose_Behar{at}brown.edu).






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