Some steric factors affecting smooth muscle relaxation by cAMP analogs.

The inhibitory potency of equimolar concentrations of cyclic adenosine monophosphate (cAMP) and three of its butyrylated derivatives; N6, O2'-dibutyryl cAMP (DBcAMP), N6-monobutyryl cAMP (N6MBcAMP) and O2' monobutyryl cAMP (O2' MBcAMP) was determined in isolated guinea pig ileal and aortic smooth muscle. Substitution in the N6 position did not markedly alter the inhibitory action of cAMP in these smooth muscles. However, an increase in the effectiveness of low concentrations of epinephrine in aorta was noted in the presence of the N6 substituted derivatives (0.1 mM). Addition of a butyryl group to the O2' position greatly decreased the activity of cAMP in both intestinal and vascular smooth muscle. The character of smooth muscle relaxation shown by cAMP and its analogs is very similar to that shown by adenosine and its analogs. These substances all appear to be acting in the same manner to relax intestinal and aortic smooth muscle.