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POTENTIATION BY DILAZEP OF THE NEGATIVE INOTROPIC EFFECT OF ADENOSINE ON GUINEA‐PIG ATRIA
Author(s) -
FUJITA SHINJI,
ISHIDA YUKIO,
IZUMI KYOKO,
MORITOKI HIDEKI,
OHARA MASAYUKI,
TAKEI MASAO
Publication year - 1980
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1980.tb10423.x
Subject(s) - adenosine , inotrope , long term potentiation , guinea pig , medicine , pharmacology , chemistry , receptor
1 Dilazep, a coronary dilator, has been reported to potentiate the negative inotropic and negative chronotropic responses of guinea‐pig atria to adenosine. Studies were made on the mechanism of the potentiating action of dilazep with special reference to the degradation and uptake of adenosine. 2 The negative inotropic actions of adenosine and adenine nucleotides, such as ATP, ADP, AMP and cyclic AMP, on guinea‐pig atria were selectively and dose‐dependently augmented by dilazep at concentrations insufficient to produce any effect alone (0.01 to 1 μ m ). 3 Incubation of atrial tissue with 8.8 n m adenosine, containing 0.1 μCi of [ 3 H]‐adenosine, resulted in accumulation of [ 3 H]‐adenosine in the tissue; dilazep (0.01 to 1 μ m ) inhibited this accumulation. 4 Adenosine (10 μ m to 10 m m ) was degraded to inosine and hypoxanthine during incubation with atrial tissue; dilazep (0.1 to 10 μ m ) retarded the disappearance of adenosine and the formation of inosine and hypoxanthine. 5 These results suggest that dilazep potentiates the negative inotropic effect of adenosine on guinea‐pig atria by preventing both its accumulation by atrial tissue and degradation by deaminase.