ON THE MECHANISM WHEREBY CERTAIN NUCLEOTIDES PRODUCE CONTRACTIONS OF SMOOTH MUSCLE

Abstract

The mechanism of the contractile actions of adenine nucleotides on rat uterine muscle has been analyzed. ATP and ADP were about equally effective in causing contraction and much more effective than AMP and adenosine. Orthophosphate and pyrophosphate were less effective. None of the nucleotides caused inhibition of contraction to other drugs such as acetylcholine. Neither selective inhibition of known receptors nor depolarization by K₂SO₄ prevented these contractions, but calcium depletion sufficient to prevent acetylcholine contractions prevented ATP and ADP contractions. Metabolic inhibitors also produced parallel depression of responses to acetylcholine and the nucleotides.The possibility was entertained that these nucleotides might have acted by virtue of their ability to complex magnesium present in the cell membrane, thereby favoring calcium entry and contraction; hence a variety of experiments were done to test this hypothesis. Concentrations of calcium and magnesium, either when the cations were free in the bath solution or when they were complexed with ATP, were varied and the effects on contraction noted. The results were consistent with the hypothesis. Substitution of strontium for calcium enhanced the effectiveness of ATP in evoking contractions.