Interaction of cinepazide with adenosine on guinea-pig atria.

The negative inotropic effects of adenosine and adenine nucleotides, such as ATP and cAMP, on guinea-pig atria were selectively and dose-dependently augmented by cinepazide in concentrations insufficient to produce any effect alone (3 X 10(-5) M-3 X 10(-4)M). Adenosine (10(-5) M, 10 microCi) was degraded to inosine and hypoxanthine during incubation with atrial tissue. Cinepazide (3 X 10(-4) M) retarded the degradation of adenosine, and the formation of inosine and hypoxanthine. Incubation of the atrial tissue with adenosine (8.1 X 10(-9) M, 0.1 microCi) resulted in accumulation of 3H-activity. Cinepazide (3 X 10(-5) M-3 X 10(-4) M) inhibited this accumulation. These results suggest that cinepazide potentiates the negative inotropic effect of adenosine on guinea-pig atria by preventing both its degradation by deaminase and its accumulation by atrial tissue.