MECHANISM OF THE POSITIVE INOTROPIC ACTION OF PURINE NUCLEOSIDES IN ISOLATED ATRIA

¹ Departments of Pharmacology and Pathology, Albany Medical College, Albany, New York

This investigation has shown that a purine nucleoside can possess both positive and negative inotropic properties depending on the dose employed. The positive inotropic property of one such purine nucleoside, guanosine, appears to be mediated through the release of heart catecholamines. The storage sites from which these catecholamines are mobilized would seem to be the same one acted upon by tyramine. Neither the positive nor the negative inotropic effects of guanosine are affected by atropine and appear to be independent of the release of acetylcholine.

Study of structural variants of guanosine, including guanine, deoxyguanosine and 6-thio-guanosine indicate that the intact sugar moietyof the purine nucleoside is necessary for greatest cardiac effect.