Advertisement

Polyamine effects on human myometrial contractility

      Abstract

      Objective: This study was undertaken to investigate the effects of the polyamine spermine on human uterine contractility. Study design: Under physiologic conditions, an isometric tension recording was performed in isolated myometrial strips from biopsy specimens obtained at elective cesarean delivery (n = 24 specimens) and from premenopausal hysterectomy specimens (n = 6 specimens). The effects of spermine (1 μmol/L-10 mmol/L in cumulative doses) on spontaneous, agonist-induced myometrial contractions were measured, and dose response curves were constructed. The pD2 (−log EC50) values and the maximal inhibition values achieved were compared for spontaneous and agonist-induced contractions. Results: Spermine exerted a potent relaxant effect on all spontaneous and agonist-induced myometrial contractions, with mean maximal inhibition values between 62.8% ± 4.3% and 91.4% ± 1.8% and pD2 values between 2.66 ± 0.23 and 4.01 ± 0.20. Its inhibitory effect varied significantly with different contraction types (pD2, P < .05; mean maximal inhibition, P < .001), and it was least potent on BAY K 8644-elicited contractions (pD2, P < .05; mean maximal inhibition, P < .01). Conclusion: The polyamine spermine exerts a potent relaxant effect on human uterine tissue. This effect appears to be mediated, at least partially, by calcium antagonism. Polyamines may play a role in the maintenance of uterine quiescence during pregnancy. (Am J Obstet Gynecol 2002;186:778-83.)

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to American Journal of Obstetrics & Gynecology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Phillippe M
        • Chien EK
        Intracellular signaling and phasic myometrial contractions.
        J Soc Gynecol Invest. 1998; 5: 169-177
        • Goldenburg RL
        • Rouse DJ
        Prevention of premature birth.
        N Engl J Med. 1998; 339: 313-320
        • Morrison JJ
        • Rennie JM
        Clinical, scientific and ethical aspects of fetal and neonatal care at extremely preterm periods of gestation.
        Br J Obstet Gynaecol. 1997; 104: 1341-1350
        • Igarashi K
        • Kashiwagi K
        Polyamines: mysterious modulators of cellular functions.
        Biochem Biophys Res Commun. 2000; 271: 559-564
        • Mitchell MF
        • Tortolero-Luna G
        • Lee JJ
        • Hittleman WK
        • Lotan R
        • Wharton JT
        • et al.
        Polyamine measurements in the uterine cervix.
        J Cell Biochem Suppl. 1997; 28-29: 125-132
        • Gutierrez M
        • Fernandez AI
        • Revuelta MP
        • Cantabrana B
        • Hidalgo A
        Partial contribution of polyamines to the relaxant effect of 17α-estradiol in rat uterine smooth muscle.
        Gen Pharmacol. 1998; 30: 71-77
        • Revuelta MP
        • Cantabrana B
        • Hidalgo A
        Pharmacological evidence for the contribution of polyamines as mediators of the transcriptional component involved in smooth muscle relaxation elicited by forskolin.
        Life Sci. 1997; 61: 2443-2454
        • Morrison JJ
        • Ashford ML
        • Khan RN
        • Smith SK
        The effects of potassium channel openers on isolated pregnant human myometrium before and after onset of labor: potential for tocolysis.
        Am J Obstet Gynecol. 1993; 169: 1277-1285
        • Slattery MM
        • O'Leary MJ
        • Morrison JJ
        Effect of parathyroid hormone-related peptide on human and rat myometrial contractility in vitro.
        Am J Obstet Gynecol. 2001; 184: 625-629
        • Fernandez AI
        • Cantabrana B
        • Sanchez M
        • Hidalgo A
        Extracellular and intracellular effects of polyamines on smooth muscle contractions.
        Life Sci. 1995; 57: 855-861
        • Wing LY
        • Chan CF
        • Jiang MJ
        Acetylpolyamines decrease blood pressure, [Ca++]i and isometric force of vascular smooth muscle.
        J Pharmacol Exp Ther. 1993; 266: 179-183
        • Myung CS
        • Blankenship JW
        • Meerdink DJ
        A mechanism of vasodilatory action of polyamines and acetylpolyamines: possible involvement of their Ca2+ antagonistic properties.
        J Pharm Pharmacol. 2000; 52: 695-707
        • Williams K
        Interactions of polyamines with ion channels.
        Biochem J. 1997; 325: 289-297
        • Oliver D
        • Baukrowitz T
        • Fakler B
        Polyamines as gating molecules of inward-rectifier K+ channels.
        Eur J Biochem. 2000; 267: 5824-5829
        • Wang JY
        • Wang J
        • Golovina VA
        • Li L
        • Platoshyn O
        • Yuan JX
        Role of K(+) channel expression in polyamine-dependent intestinal epithelial cell migration.
        Am J Physiol Cell Physiol. 2000; 278: 303-314
        • Homer KL
        • Wanstall JC
        Cyclic GMP-independent relaxation of rat pulmonary artery by spermine NONOate, a diazeniumdiolate nitric oxide donor.
        Br J Pharmacol. 2000; 131: 673-682
        • Seiler N
        Polyamines.
        J Chromatogr. 1986; 379: 157-176
        • Hiramatsu Y
        • Eguchi K
        • Sekiba K
        Alterations in polyamine levels in amniotic fluid, plasma and urine during normal pregnancy.
        Acta Med Okayama. 1985; 39: 339-346
        • Bayer S
        • Raul F
        • Boehm N
        • Klein A
        • Angel F
        Modulatory effects of polyamines and GABA on rat ileal motility in vitro.
        Gastroenterol Clin Biol. 1999; 23: 824-831
        • Luckas MJ
        • Wray S
        A comparison of the contractile properties of human myometrium obtained from the upper and lower uterine segments.
        Br J Obstet Gynaecol. 2000; 107: 1309-1311