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.
1 The binding and efflux characteristics of [14C]-guanethidine and [3H]-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 [14C]-guanethidine and [3H]-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 [14C]-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 [14C]-guanethidine but not that of [3H]-noradrenaline. 5 Heart slices labelled with [3H]-noradrenaline became refractory to successive exposures to releasing agents although an appreciable amount of labelled compound was still present in in these slices. 6 It is suggested that [14C]-guanethidine and [3H]-noradrenaline are bound at a common extravesicular 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.
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites / Q000187:drug effects*; D001693:Biological Transport, Active / Q000187:drug effects; D005260:Female; D006145:Guanethidine / Q000378:metabolism*; D006321:Heart / Q000294:innervation; D066298:In Vitro Techniques; D008297:Male; D008566:Membranes / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D013268:Stimulation, Chemical; D013997:Time Factors
D000661:Amphetamine; D009638:Norepinephrine; D006145:Guanethidine