Mechanisms of the release of 3H-noradrenaline by dimethylphenylpiperazinium (DMPP) in the rat vas deferens.
In the rat vas deferens, DMPP is a substrate of uptake1 (Km = 11.5 mumol/l). 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) mumol/l DMPP induced a hexamethonium-sensitive release of 3H-noradrenaline of short duration. Hence, in the presence of extracellular calcium, 100 mumol/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 mumol/l.
Niebler
M
M
Institut für Pharmakologie und Toxikologie, Universität Würzburg, Federal Republic of Germany.
Trendelenburg
U
U
D000818:Animals; D002118:Calcium / Q000502:physiology; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D065098:Catechol O-Methyltransferase Inhibitors; D003891:Desipramine / Q000494:pharmacology; D004246:Dimethylphenylpiperazinium Iodide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006584:Hexamethonium Compounds / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014649:Vas Deferens / Q000187:drug effects / Q000378:metabolism
D065098:Catechol O-Methyltransferase Inhibitors; D006584:Hexamethonium Compounds; D008996:Monoamine Oxidase Inhibitors; D010879:Piperazines; D004246:Dimethylphenylpiperazinium Iodide; D008995:Monoamine Oxidase; D002394:Catechol O-Methyltransferase; D002118:Calcium; D003891:Desipramine; D009638:Norepinephrine