ISSN:
1432-1912
Keywords:
Amezinium
;
Rabbit heart
;
Rabbit pulmonary artery
;
Intraneuronal monoamine oxidase
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary Effects of amezinium on postganglionic sympathetic neurones were studied in the heart and pulmonary artery of the rabbit. 1. In isolated perfused hearts, amezinium increased the rate of beat. The effect was antagonized by propranolol or cocaine and by pretreatment with reserpine or 6-hydroxydopamine. 2. In hearts pre-perfused with 3H-noradrenaline, amezinium 0.003 μM reduced the outflow of 3H-DOPEG by 50%. 0.1 μM and higher concentrations in addition reduced the outflow of 3H-MOPEG and increased the outflow of 3H-noradrenaline and 3H-NMN. The outflow of 3H-DOMA and 3H-VMA was not changed. Cocaine prevented the effects of amezinium. When hearts were first perfused with amezinium and then with 3H-noradrenaline, the subsequent outflow of 3H-DOMA was abolished. 3. Hearts were perfused with 3H-noradrenaline 50 nM, and the arterio-venous difference of the 3H-amine was determined. Amezinium 0.29 μM reduced the arterio-venous difference by 50%. 4. Rabbits received intravenous injections of amezinium and were killed 30 min later. The hearts were perfused with 3H-noradrenaline. Pretreatment with amezinium 10 μg/kg diminished the outflow of 3H-DOPEG during the perfusion with 3H-noradrenaline, whereas pretreatment with 1 mg/kg was necessary to decrease the arterio-venous difference of 3H-noradrenaline. 5. Amezinium 4 μM caused 50% inhibition of MAO in crude homogenates and mitochondrial preparations from rabbit hearts, with 3H-noradrenaline as substrate. 6. In pulmonary artery strips preincubated with 3H-noradrenaline, the effects of amezinium on the outflow of 3H-compounds were similar to its effects in the heart. In addition, amezinium reduced the overflow of 3H-DOPEG and enhanced contractions elicited by electrical stimulation. 7. Amezinium is a relatively weak inhibitor of MAO in cell-free preparations. However, in the intact tissue it is a very potent inhibitor of the MAO inside noradrenergic neurones because it is concentrated in these neurones by the noradrenaline uptake mechanism. Being a substrate of uptake, amezinium also inhibits the uptake of noradrenaline. In contrast to bretylium which also inhibits intraneuronal MAO, amezinium is not an adrenergic neurone blocking agent. Concentrations higher than those needed to block intraneuronal MAO in addition release noradrenaline and thereby increase the rate of cardiac contraction.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00498425
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