PHARMACOLOGICAL CHARACTERIZATION OF PROSTANOID RECEPTORS IN NON-PREGNANT PORCINE MYOMETRIUM
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1. In order to characterize prostanoid receptors in the non-pregnant porcine uterus, effects of naturally occurring PGs (PGD<SUB>2</SUB>, PGE<SUB>2</SUB>, PGE<SUB>1</SUB>, PGF<SUB>2α</SUB>, PGI<SUB>2</SUB>) and synthetic pros-tanoid receptor agonists (cloprostenol, BW-245C, iloprost) on contractility of longitudinal (LM) and circular muscles (CM) were examined <I>in vitro</I>.2. PGD<SUB>2</SUB>, PGE<SUB>2</SUB>, PGE<SUB>1</SUB>, PGF<SUB>2α</SUB> and PGI<SUB>2</SUB> increased muscle contractility of the LM. The ranking order of potency was estimated to be PGF<SUB>2α</SUB>≥PGE<SUB>2</SUB>=PGE<SUB>1</SUB>>PGD<SUB>2</SUB>>PGI<SUB>2</SUB>. On the contrary, PGE<SUB>1</SUB> and PGE<SUB>2</SUB> inhibited the muscle contractility at a high concentration (1-10, μM)<BR>3. PGD<SUB>2</SUB> inhibited the spontaneous contractions of the CM but PGE<SUB>2</SUB>, PGE<SUB>1</SUB>, PGF<SUB>2α</SUB> and PGI<SUB>2</SUB> were less effective in causing the inhibition. The PGD<SUB>2</SUB>-induced inhibition was potentiated by Ro20-1724 but not by zaprinast. PGD<SUB>2</SUB> treatment (for 5 min) significantly increased the tissue cyclic AMP level.<BR>4. Cloprostenol (1 nM-10, μM) increased the contractility of both muscle layers but the LM was more sensitive to cloprostenol than the CM.<BR>5. BW-245C (1 nM-10 μM) inhibited the spontaneous contractions of both muscle layers but the inhibition in the CM was more conspicuous than that in the LM.<BR>6. Iloprost (10 nM-10, μM) increased the contractility of both muscle layers and these responses were not antagonized by SC19220 (5 μM).<BR>7. Indomethacin (100 nM for 60 min) significantly decreased the frequency of spontaneous contractions in the LM. But spontaneous contractions in the CM were quitely insensitive to indomethacin.<BR>8. The present results suggest that contractile (FP, EP<SUB>3</SUB>) and relaxatory (DP, EP2/EP4) prostanoid receptors are present in the porcine myometrium in a muscle layer-dependent manner (FP, LM>CM DP, CM>LM). Endogeneous PGs involve in the initiation of spontaneous contractions in the LM.
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