RECEPTOR SUBTYPES INVOLVED IN DUAL EFFECTS INDUCED BY PROSTAGLANDIN E(2) IN CIRCULAR SMOOTH-MUSCLE FROM DOG COLON

Smooth muscle strips and isolated muscle cells from the circular layer of dog colon, were used to study the effect of prostaglandin E(2) (PG E(2)) and their analogs acting at EP receptors: Iloprost (IP/EP(1)), b utaprost (EP(2)) and enprostil (EP(3)) and SC19220 (antagonist EP(1)) to characterize the EP-receptors involved in the control of muscle fun ction. In strips treated with tetrodotoxin, only enprostil provoked a concentration-dependent contraction. The concentration of enprostil in ducing a half maximal contraction (EC(50)) was 400 nM and the maximal effect was obtained at 1 mu M. PGE(2), butaprost and iloprost induced a dose-dependent relaxation, with an EC(50) of 200, 80 and 200 nM, res pectively. The maximal relaxation was obtained at 1 mu M for all these agents. When the EP(1) antagonist, SC19220 (10 mu M), was added 20 mi n before PGE(2) or their analogs, their respective concentration-respo nse curves were not affected. in isolated cells, PGE(2) and enprostil induced a cell contraction in a concentration-dependent manner, wherea s iloprost and butaprost had no effect by themselves. The maximal cont raction was 24.1 +/- 1.7% at 10 nM PGE(2) and 22.5 +/- 1.6% at 10 nM e nprostil. EC(50) of PGE(2) and enprostil was 40 pM. SC 19220, at conce ntrations ranging from 1 pM to 0.1 mu M, failed to inhibit the contrac tion induced by either PGE(2) or enprostil. When cells were preincubat ed for 1 min with butaprost or iloprost at concentrations ranging from 1 pM to 1 mu M, the contraction induced by CCK8 (10 nM) was inhibited in a concentration-dependent manner. EC(50) of butaprost and iloprost in inducing cell relaxation was 5 pM and 100 pM, respectively. Additi on of SC19220 (10 mu M) failed to inhibit this relaxation. We conclude that, circular smooth muscle cells from dog proximal colon express tw o PGE(2) receptor subtypes, inducing opposite effects: EP(3) receptors mediating a cell contraction and EP(2) receptors mediating a cell rel axation.