Summary
In the rat vas deferens, DMPP is a substrate of uptake, (Krn = 11.5 μmol/I). After block of vesicular uptake, monoamine oxidase and catechol-O-methyl transferase, after loading of the tissue with 3H-noradrenaline, and in calcium-free solution (i. e., when axoplasmic 3H-noradrenaline levels were high and when depolarization-induced exocytotic release was impossible), DMPP induced a pronounced outward transport of 3H-noradrenaline. On the other hand, when, in similar experiments, vesicular uptake and monoamine oxidase were intact (i.e., when axoplasmic 3H-noradrenaline levels were low), DMPP induced very little outward transport of 3H-noradrenaline. This discrepancy indicates that DMPP has little ability to mobilize vesicularly stored 3H-amine.
When the medium contained calcium (catechol-O-methyl transferase inhibited, all other mechanisms intact), 100 (but not 10) μmol/l DMPP induced a hexamethonium-sensitive release of 3H-noradrenaline of short duration. Hence, in the presence of extracellular calcium, 100 μmol/l DMPP elicits exocytotic release via activation of hexamethonium-sensitive nicotinic acetylcholine receptors.
DMPP inhibits the monoamine oxidase of rat heart homogenate with an IC50 of about 100 μmol/l.
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Abbreviations
- COMT:
-
catechol-O-methyl transferase
- DMPP:
-
dimethylphenylpiperazinium
- DOMA:
-
dihydroxymandelic acid
- DOPEG:
-
dihydroxyphenylglycol
- MAO:
-
monoamine oxidase
- NMN:
-
normetanephrine
- OM-fraction:
-
column chromatographic fraction containing all O-methylated 3H-metabolites
- OMDA:
-
fraction containing O-methylated and deaminated metabolites
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Niebler, M., Trendelenburg, U. Mechanisms of the release of 3H-noradrenaline by dimethylphenylpiperazinium (DMPP) in the rat vas deferens. Naunyn-Schmiedeberg's Arch Pharmacol 341, 43–49 (1990). https://doi.org/10.1007/BF00195056
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DOI: https://doi.org/10.1007/BF00195056