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Selective depletion of noradrenaline: a proposed mechanism of the adrenergic neurone‐blocking action of bretylium
Author(s) -
ABBS E. T.,
ROBERTSON M. I.
Publication year - 1970
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.1476-5381.1970.tb09887.x
Subject(s) - bretylium , chemistry , adrenergic , endocrinology , medicine , blockade , stimulation , pharmacology , biochemistry , receptor
Summary1 The effects of bretylium have been investigated on the content and subcellular distribution of noradrenaline in cat spleen and on the overflow of noradrenaline in response to stimulation of the splenic nerve. 2 Bretylium, 15 min after its administration, produces a significant depletion of noradrenaline in only the supernatant fraction of an homogenate; at this time adrenergic neurone blockade is evident. This depletion of noradrenaline is apparent up to 18 h later but has disappeared 7 days after the administration of bretylium when nerve function is also restored. 3 Both the development of the neurone blockade and the depletion of noradrenaline are prevented by previous administration of (+)‐amphetamine. 4 In bretylium‐pretreated cats the noradrenaline content of the supernatant fraction is replenished and the neurone blockade is abolished after treatment with (+)‐amphetamine. 5 The depletion of noradrenaline, which is evident 30 min, 60 min and 18 h after treatment with bretylium, from other subcellular fractions—especially the high‐speed particulate fraction—appears to be unassociated with adrenergic neurone blockade. 6 It is concluded that bretylium produces its adrenergic neurone‐blocking activity by depleting noradrenaline from a “store” whose amine appears in the supernatant fraction after homogenization. Whilst bretylium is present this “store” cannot refill with noradrenaline.