6533b831fe1ef96bd12998a6

RESEARCH PRODUCT

Autoinhibition of nicotinic release of noradrenaline from postganglionic sympathetic nerves

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1. The effects of nicotine, DMPP (1,1-dimethylphenylpiperazine) and acetylcholine (plus atropine) on the isolated rabbit heart were investigated. Heart rate, amplitude of contraction, coronary flow and output of noradrenaline into the perfusate were recorded. Noradrenaline was estimated fluorimetrically. 2. All nicotinic drugs evoked a dose-dependent output of noradrenaline and increased the rate and the amplitude of contraction. Increases of heart rate in response to nicotine and DMPP and increases of amplitude of contraction in response to all nicotinic drugs were clearly related to the output of noradrenaline. 3. The dose-response curves of the noradrenaline output evoked by nicotine, DMPP and acetylcholine (plus atropine) were steeply rising and parallel. The concentrations of DMPP, nicotine and acetylcholine (plus atropine) needed to cause a half-maximal noradrenaline output were in the proportions 1∶ 1.1∶ 5.2 respectively. 4. During infusion of nicotinic drugs the noradrenaline output rose to its maximum within 30 sec and then declined exponentially. The rate constant of the decline was not significantly different from the rate constant of the slow phase of washout of exogenously administered noradrenaline. 5. Atropine (which facilitates) and hexamethonium (which blocks the noradrenaline output evoked by acetylcholine) were effective only in the first 5–10 sec of the infusion of acetylcholine. 6. The threshold concentrations for nicotine or acetylcholine (plus atropine) required to cause a noradrenaline output on the one hand, and to cause autoinhibition on the other hand, were identical. 7. It is concluded that nicotinic drugs cause an “explosive” release of noradrenaline from the adrenergic terminal fibres into the extraneuronal space. The rapid termination of this release is caused by sudden autoinhibition.