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Differential effects of D600, nifedipine and dantrolene sodium on excitation‐secretion coupling and presynaptic β‐adrenoceptor responses in rat atria
Author(s) -
Callanan K.M.,
Keenan A.K.
Publication year - 1984
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.1476-5381.1984.tb16240.x
Subject(s) - isoprenaline , nifedipine , dantrolene , dantrolene sodium , chemistry , endocrinology , calcium , medicine , propranolol , stimulation , extracellular , depolarization , calcium channel , biochemistry , organic chemistry
1 The stimulation‐evoked release of tritium was measured from rat atria labelled with [ 3 H]‐noradrenaline. The calcium dependence of evoked release and the facilitation of this release via activation of presynaptic β‐adrenoceptors were examined using D600 (methoxyverapamil), nifedipine and dantrolene sodium. 2 Both D600 and nifedipine at dose levels of 20 and 100 μ m inhibited evoked release. Dantrolene (20, 100 μ m ) reduced release by 25%, the effect being maximal at 20 μL m . 3 In the presence of 20 n m isoprenaline, a facilitation of evoked release occurred, which was blocked by 0.1 μ m (—)‐propranolol. 4 The facilitatory action of isoprenaline was abolished by omission of calcium from the buffer, or by D600 or nifedipine, (100 μ m ). In contrast, the response to isoprenaline was not modified by dantrolene (20, 100 μ m ). 5 It is concluded that (a) the evoked release of noradrenaline (NA) utilizes Ca from both intra‐ and extracellular sources and that (b) isoprenaline increases NA secretion by promoting the depolarization‐induced influx of Ca.