This study investigates the pronounced synergism between the weak contractile action of prostaglandin E2 (PGE2) and strong actions of phenylephrine, U-46619 and K+ on rat isolated femoral artery. The potency ranking for synergism was SC-46275 (prostanoid receptor agonist selectivity: EP3⪢EP1)=sulprostone (EP3>EP1)>17-phenyl PGE2 (EP1>EP3). The novel EP3 antagonist L-798106 (0.2–1 μM) blocked the enhanced action of sulprostone (pA2=7.35–8.10), while the EP1 antagonist SC-51322 (1 μM) did not (pA2<6.0). Matching responses to priming agent and priming agent/sulprostone were similarly suppressed by nifedipine (300 nM) and the selective Rho-kinase inhibitors H-1152 (0.1–1 μM) and Y-27632 (1–10 μM). Our findings implicate an EP3 receptor in the prostanoid component of contractile synergism. While the synergism predominantly operates through a Ca2+ influx–Rho-kinase pathway, the EP3 receptor does not necessarily transduce via Rho-kinase.
|Number of pages||5|
|Journal||Prostaglandins, Leukotrienes and Essential Fatty Acids|
|Publication status||Published - 2006|
- prostaglandin e2