Investigation of the pronounced synergism between prostaglandin e2 and other vasoconstrictor agents on rat femoral artery

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.