Regulation of connexin 43 by nitric oxide in primary uterine myocytes from term pregnant women.

OBJECTIVE: Our purpose was to test the hypothesis that nitric oxide signals regulate the expression of the gap-junction protein connexin 43 in primary uterine myocytes from pregnant women at term.

STUDY DESIGN: Northern analysis and immunoblotting were used to determine the expression of connexin 43 in myocytes cultured in the presence of the nitric oxide donors S -nitroso-N -acetyl-penicillamine (SNAP) (100 micromol/L) and (Z)-1-[2-(2-aminoethyl)-N -(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate diethylenetriamine (NOC-18) (100 micromol/L). We also tested the effect of the NO stimulants 8-bromo-cyclic adenosine 3',5'-monophosphate (cAMP) (100 micromol/L) and 8-bromo-cyclic guanosine 3',5'-monophosphate (cGMP) (200 micromol/L), and the nitric oxide synthase inhibitors N -nitro-L-arginine methyl ester (NAME) (100 micromol/L) and L -N (1-iminoethyl)lysine (NIL) (50 micromol/L).

RESULTS: Nitric oxide and 8-bromo-cAMP reduced the level of connexin 43 expression, and 8-bromo-cGMP had no effect. In contrast, NIL, but not NAME, increased the levels of connexin 43 protein without affecting the level of connexin 43 messenger RNA. With immunoblotting, expression of inducible nitric oxide synthase was not detected in these cells.

CONCLUSION: Nitric oxide down-regulates the expression of connexin 43 in cultured human myocytes. We speculate that this effect may decrease the efficacy of intermyocyte signaling and thus contribute to uterine quiescence during human pregnancy.