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High and concentration‐proportional accumulation of [ 3 H]‐nitrendipine by intact cardiac tissue
Author(s) -
Lüllmann Heinz,
Mohr Klaus
Publication year - 1987
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.1476-5381.1987.tb11207.x
Subject(s) - nitrendipine , inotrope , chemistry , biophysics , extracellular , endocrinology , biochemistry , biology , calcium , organic chemistry
1 The binding of [ 3 H]‐nitrendipine to intact, electrically driven isolated left atria of guinea‐pigs was investigated over the concentration range 10 −10 m to 3 × 10 −5 m . 2 A high affinity binding site saturable in the n m range as found in ventricular homogenates could not be detected. Instead the accumulation of nitrendipine in intact atria was found to be proportional to the concentration from 10 −10 m to 10 −6 m ; beyond 10 −6 m the binding started to become saturated. 3 Nitrendipine was highly accumulated in atrial tissue. The cell: medium ratios amounted to about 120 in the range from 10 −10 m to 10 −6 m . 4 The concentration‐response curve for the negative inotropic action of nitrendipine yielded an ED 50 of 3 × 10 −7 m , thus lying within the range of concentration‐proportional accumulation. 5 The reduction of the contractile force proceeded faster ( t 1/2 10 min) than the uptake process ( t 1/2 ∼ 40 min) suggesting that it is the binding of nitrendipine into a superficial compartment, which interferes with the excitation‐contraction coupling. 6 The results suggest that the high concentration of nitrendipine present in hydrophobic cellular compartments such as the plasmalemma might be involved in its pharmacological action.