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

Authors:
  • RLR. Loutzenhiser
    R. Loutzenhiser
  • CBC. van Breemen
    C. van Breemen
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Abstract
The effects of a stable analog 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 analog 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 analog 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 analog-induced contractions in Ca2+-free media were also prevented by prior exposure to histamine but not angiotensin II. D-600 [.alpha.-isopropyl-.alpha.[(N-methyl-N-homoveratryl)-.gamma.-aminopropyl]3,4,5-trimethoxyphenylacetonitrile] completely blocked the U-44069-induced gain in Ca content (IC50 = 10-6 M) but inhibited the contractile response by only 40%. The PGH2 analog apparently 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.