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Effects of manganese on cyclic GMP levels in the rat ductus deferens

  • Klaus-Dieter Schultz
  • Karin Schultz
  • Günter Schultz
Article

Summary

Mn2+ and other divalent cations (Me2+) are capable of preventing contractile responses of smooth muscle to various stimuli. The effects of Mn2+, of other inhibitory Me2+ and of Ca2+ on basal and hormone-stimulated cyclic nucleotide levels were studied in the ductus deferens of the rat.

In tissue segments that had been preincubated with no Me2+ added, Mg2+ (2 or 10 mM), Co2+, Ni2+ and Cd2+ (2 mM each) caused 2-fold elevations of the cyclic GMP level within 5 min, whereas Mn2+ and Ca2+ caused 7-and 5-fold elevations, respectively. Cyclic AMP levels were not significantly changed except for a 10–20% increase by Mn2+. Whereas Mn2+ caused a continuous rise of the cyclic GMP level over at least 10 min, the stimulatory effect of Ca2+ was most pronounced during the first minute. The effects of Ca2+ and Mn2+ were not additive. When Ca2+ was added with or after Mn2+ (2 mM each), the stimulatory effect of Mn2+ was depressed. Similarly, Mn2+ caused only a small increase in the cyclic GMP level of tissue incubated with Ca2+.

With the hormonal stimuli, acetylcholine and noradrenaline (0.1 mM each), a dissociation of their effects on tissue tone and on the cyclic GMP level occurred. Whereas either stimulus caused about 2-fold elevation of the cyclic GMP in the presence of Mn2+ with or without Ca2+ present, contractile responses were prevented by Mn2+. In contrast, K+ at a high, depolarizing concentration, which increased the cyclic GMP level in the presence of Ca2+, had no effect on the cyclic nucleotide with Mn2+ added instead of Ca2+. Whereas hormone-induced elevations of the cyclic GMP level depended on the presence of Me2+, the effect of hydroxylamine (0.1 mM) to increase the level of this nucleotide in the absence of Me2+ was not augmented by Ca2+ or Mn2+.

The present data indicate that hormone-induced elevations of the cyclic GMP level in the absence of extracellular Ca2+ do not promote contraction. The findings also suggest that hormones are capable of stimulating cyclic GMP formation by mechanisms other than hormone-induced increase in cytoplasmic Ca2+ concentration.

Key words

Divalent cations Calcium Manganese Cyclic GMP Smooth muscle 

Abbreviations

cGMP

cyclic

GMP

guanosine 3′:5′-monophosphate

cAMP

cyclic AMP, adenosine 3′:5′-monophosphate

Me2+

divalent cation(s)

EDTA

ethylenediaminetetraacetic acid

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Copyright information

© Springer-Verlag 1977

Authors and Affiliations

  • Klaus-Dieter Schultz
    • 1
  • Karin Schultz
    • 1
  • Günter Schultz
    • 1
  1. 1.Pharmakologisches Institut der Universität HeidelbergHeidelbergGermany

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