EFFECT OF ADENOSINE ANALOGS ON ISOLATED INTESTINE AND UTERUS

¹ Institute of Pharmacology, University of Milan, Italy, and Division of Experimental Chemotherapy, Sloan-Kettering Institute for Cancer Research, New York, New York

Adenosine and its 2-chloro, 2-methyl, 2-hydroxy, and 2-amino derivatives have been shown to cause with different degrees of potency a transient reduction of tone and spontaneous motility in the isolated intestine of rabbit; the 2-acetamido derivative has been relatively inactive. After recovery from the effects caused by any of the active compounds, preparations did not respond to succeeding doses of either adenosine or any of its 2-substituted derivatives. Inosine, an end product of adenosine deamination, proved neither active in reducing contractility nor effective in inducing refractoriness to the action of adenosine.

The effects of adenosine-5-monophosphate (AMP) and adenosine-triphosphate (ATP) have been found to be similar to those of adenosine in the isolated intestine of rabbits. However, the nucleotide, ATP, and adenosine did not evince the same type of reciprocal inhibition which has been demonstrated among members of the series of active purine ribosides.

On the isolated intestine of guinea pig only adenosine, 2-chloroadenosine, AMP, and ATP were found effective against histamine-induced spasm; the same agents were inactive against acetylcholine-induced spasm.

On the isolated uterus of the virgin guinea pig the activity of 2-chloro-adenosine was found to be similar to that of adenosine.

These findings have been discussed with reference to previous observations of the relative hypotensive activities of adenosine and its 2-substituted derivatives.