Mg2+–Ca2+–Na+ interactions in uterine smooth muscle: Studies with cAMP

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Abstract
The influence of variation in the extracellular concentrations of Na+, Mg2+, and Ca2+ in the depolarizing medium on isoproterenoi-induced increases in cAMP levels and relaxation was studied in rat uterus. Isoproterenol (10−8 M) failed to increase cAMP levels in the high-K+ medium containing no Na+. When 80 mM Na+ was present in the medium, isoproterenol caused increases in cAMP levels similar to those observed in nondepolarized uterus. A similar effect of 2.5 mM Mg2+ was observed on the cAMP response. These effects of Na+ and Mg2+ were antagonized by increasing the extracellular concentration of Ca2+. The simultaneous presence of 80 mM Na+ and 2.5 mM Mg2+ did not produce an additive effect on the cAMP responses. The relaxation responses to isoproterenol were not significantly altered in the above experiments. The results are consistent with our previous suggestion that the observed effect of Na+ and Mg2+ on the cAMP response is mediated indirectly by inhibiting Ca influx occurring during depolarization.

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