Submitted on May 14, 2009
Revised on August 17, 2009
Accepted on September 1, 2009
Effects of Progesterone on Motility and Prostaglandin Levels in the Distal Guinea Pig Colon
Zuo Liang Xiao1, Piero Biancani2, and Jose Behar2*
1 Rhode Island Hospital
2 Brown University
* To whom correspondence should be addressed. E-mail: jose_behar{at}brown.edu.
BACKGROUND: Progesterone (P4) inhibits the gastrointestinal muscle contraction by downregulating G
q/11 proteins that mediate contraction, by upregulating Gs proteins that mediate relaxation and by altering the pattern of COX enzymes and prostaglandins. AIM: To examine whether P4 treatment of guinea pigs in vivo affects basal colon motility (BMI) by altering the levels and actions of PGF2 and PGE2. METHODS: Guinea pigs were treated with IM progesterone for 4 days. The BMI, the PGF2 induced contraction and PGE2 induced relaxation were examined in muscle strips and cells. The levels of PGF2 and PGE2 were measured by radioimmunoassay. RESULTS: Treatment with P4 reduced the BMI, the levels of PGF2 and PGF2 induced contraction. P4 increased PGE2 levels and PGE2 induced relaxation. Pretreatment with IM RU-486 (10 mg/kg/day), a P4 receptor antagonist, 1 h prior to P4 blocked the actions of P4. The PGF2 antagonist Al-1180 abolished BMI and PGF2 induced contraction. NEM, that block unoccupied membrane receptors, blocked Ach and VIP actions but had no effect on PGF2 and PGE2 effects. A COX-1 inhibitor decreased and a COX-2 inhibitor increased PGF2levels, GTP
S increased and GDP
S decreased the levels of PGF2. Gq/11 protein antibodies (Abs) reduced PGF2 levels and Gi3 Abs blocked its motor actions. Gs Abs increased PGF2but decreased PGE2 levels. CONCLUSION: P4 decreases BMI by reducing PGF2 levels caused by downregulation of Gq/11 and PGF2 induced contraction was blocked by down regulating Gi3. P4 also decreased the BMI by increasing PGE2 levels and PGE2 induced relaxation by upregulating Gs proteins.
