Abstract

Isolated circular smooth muscle cells from the rabbit distal colon were used to study the effect of prostaglandin E2 (PGE2) on bethanechol-stimulated smooth muscle cell contraction. Contraction was expressed as the percentage decrease in mean cell length compared with unstimulated cells. Incubation with different concentrations of PGE2 (10(-10)-10(-6) M) did not cause contraction or relaxation of unstimulated smooth muscle cells. Bethanechol stimulated a dose-dependent contraction that was maximal at 30 s. The threshold for bethanechol-stimulated contraction was 10(-11) M; the ED50 was 10(-10) M; and the maximum contraction (23.0 +/- 1.8%) occurred at 10(-8) M. Preincubation with PGE2 reduced both the efficacy and potency of bethanechol-stimulated contraction. Preincubation with 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP) or dibutyryl-cAMP reduced the efficacy of bethanechol-stimulated contraction without affecting potency. Increasing concentrations of PGE2 stimulated a dose-dependent increase in the production of intracellular cAMP (P less than 0.05). These studies show that PGE2 inhibits bethanechol-stimulated contraction of isolated colonic circular myocytes and is associated with increased production of intracellular cAMP. There is also a cAMP-independent effect of PGE2 on the potency of bethanechol stimulation.

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