Administration of E2 is known to increase sensitivity of myometrium to contractile stimuli, that are mediated by an increase of intracellular Ca2 (Cai2+). Recently discovered nucleotide, cADPR, was shown to promote smooth muscle contraction. We investigated whether administration of E2 to ovarectomized (OVX) rats changes activity of ADP-ribose cyclase, an enzyme that catalyzes synthesis of cADPR from β-NAD in uterus. OVX rats were injected with E2 (200 μg/kg/day for 7 days, s.c.), and ADPR cyclase activity was determined in homogenates from uterus by measurement of cADPR synthesis from β-NAD. In uteri from E2-rats cADPR synthesis was greatly (> Δ + 300%) increased. cADPR (nmol/mg protein); mean ± SEM controls: 1.5 ± 0.1 (4); E2-treated: 6.5 ± 0.5(4); (P < 0.05) Authenticity of cADPR product was verified with the use of sea urchin homogenate bioassays. Tamoxifen, E2-receptor antagonist (8 mg/kg/day), blocked stimulatory effect of E2 upon uterine ADPR-cyclase. Conclusions: a) E2 stimulates, via action on its receptor, activity of ADPR-cyclase in uterus; b) E2 is the first hormone found to increase cADPR synthesis in vivo; c) we surmise that increased cADPR generation caused by E2 may be the main or contributing factor that accounts for enhanced Cai2+ release and contractility of uterus in response to oxytocin and prostaglandin F2α.
|Original language||English (US)|
|State||Published - Dec 1 1997|
ASJC Scopus subject areas
- Molecular Biology