Mechanism of activation of isolated rabbit aorta by PGH2 analogue U-44069

The effects of a stable analogue of PGH2 on 45Ca fluxes and tension were studied in the isolated rabbit aorta. U-44069 produced maximal tension responses at a concentration of 10(-7) M. The analogue increased smooth muscle Ca2+ content and increased the unidirectional 45Ca influx. U-44069 also induced contractions of reduced magnitude in the absence of external Ca2+ and caused a transient stimulation of 45Ca efflux, suggesting that the analogue releases intracellularly bound Ca2+. Both the contractile response in CA2+-free media and the stimulation of 45Ca efflux were greatly attenuated by prior exposure to norepinephrine. The analogue-induced contractions in Ca2+-free media were also prevented by prior exposure to histamine but not angiotensin II. D-600 completely blocked the U-44069-induced gain in calcium content (IC50 = 10(-6) M) but inhibited the contractile response by only 40%. It was concluded that the PGH2 analogue activates rabbit aorta by activating a CA2+ influx pathway and releasing a fraction of the intracellular Ca2+ pool that is sensitive to norepinephrine and other agonists.