Abstract
We synthesized several 2- and 8-substituted derivatives of adenosine 3', 5'-cyclic monophosphate (c-AMP), and examined the effects of these compounds on the isolated atrial muscle preparation of the guinea pig. We found that several 8-substituted c-AMPs could produce definite positive inotropic and chronotropic effects, even when applied from outside the cell, while all the 2-substituted c-AMPs produced negative inotropic and chronotropic effects. Pretreatment of the preparation with aminophylline resulted in a potentiation of the positive inotropic and chronotropic effects of 8-substituted c-AMPs, while the negative inotropic and chronotropic effects of 2-substituted c-AMPs were abolished. The mechanisms by which these effects were produced are discussed.
