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EXTRA‐VESICULAR BINDING OF NORADRENALINE AND GUANETHIDINE IN THE ADRENERGIC NEURONES OF THE RAT HEART: A PROPOSED SITE OF ACTION OF ADRENERGIC NEURONE BLOCKING AGENTS
Author(s) -
GIACHETTI A.,
HOLLENBECK R.A.
Publication year - 1976
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.1476-5381.1976.tb08616.x
Subject(s) - guanethidine , nialamide , reserpine , chemistry , efflux , adrenergic , adrenergic neurons , pharmacology , endocrinology , norepinephrine , iproniazid , medicine , biochemistry , biology , monoamine oxidase , receptor , dopamine , stimulation , enzyme
1 The binding and efflux characteristics of [ 14 C]‐guanethidine and [ 3 H]‐noradrenaline were studied in heart slices from rats which were pretreated with reserpine and nialamide. 2 Binding of both compounds occurred at extra‐vesicular sites within the adrenergic neurone. After a brief period of rapid washout, the efflux of [ 14 C]‐guanethidine and [ 3 H]‐noradrenaline proceeded at a steady rate. The efflux of both compounds appeared to occur from a single intraneuronal compartment. 3 (+)‐Amphetamine accelerated the efflux of [ 14 C]‐guanethidine and [ 3 H]‐noradrenaline; this effect was inhibited by desipramine. 4 Unlabelled guanethidine and amantadine also increased the efflux of labelled compounds. Cocaine in high concentrations increased slightly the efflux of [ 14 C]‐guanethidine but not that of [ 3 H]‐noradrenaline. 5 Heart slices labelled with [ 3 H]‐noradrenaline became refractory to successive exposures to releasing agents although an appreciable amount of labelled compound was still present in the slices. 6 It is suggested that [ 14 C]‐guanethidine and [ 3 H]‐noradrenaline are bound at a common extra‐vesicular site within the adrenergic neurone. Binding of guanethidine to the extra‐vesicular site may be relevant to its pharmacological action, i.e., the blockade of adrenergic transmission.