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Interaction between Sympathomimetic Amines, Norepinephrine, Tyramine and Dopamine at the Monoamine Transporter in Sympathetic Nerve Terminals and the Role of Nitric Oxide
Author(s) -
Simaan Joseph
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.827.14
Subject(s) - chemistry , tyramine , norepinephrine transporter , monoamine neurotransmitter , norepinephrine , dopamine , methoxamine , endocrinology , medicine , nitric oxide , catecholamine , pharmacology , agonist , serotonin , receptor , biochemistry , organic chemistry
We previously showed that fresh synthesis of nitric oxide (NO) is involved in the transport of sympathomimetic amines, norepinephrine, tyramine, ephedrine and mephentermine across the monoamine transporter (MAT) in sympathetic nerve terminals and also in the blockade of the transporter by cocaine, imipramine, methylphenidate and atomoxetine. This study explored the effect of NO on the transport of dopamine (DA) and compared it with its effect on the transport of norepinephrine (NE), directly–acting on adrenergic receptors, tyramine (T), indirectly–acting by releasing norepinephrine from vesicles in sympathetic nerve terminals and methoxamine (M), not a substrate of MA transporter. Synthesis of NO was blocked with Nw‐nitro‐L‐arginine (L‐NNA) and the rise in arterial pressure it induces was reduced to starting level by restoring the basal concentration of NO through an infusion of nitroglycerin, an NO donor, thus observing the effect of fresh synthesis of NO. Anesthetized Sprague‐Dawley rats were used in which mean arterial pressure was measured. The pressor effect of single doses of NE (0.05, 0.1, 0.2 μg) was potentiated by 44–23% (P< 0,000), of T (0.025, 0.05. 0.1 mg) was reduced by 31–23% (P<0.001) and of DA (5, 10, 15μg) was reduced by 47–41% (P<0.002). The pressor effect of M was not affected. It is concluded that fresh synthesis of NO is significantly involved in the transport of NE, T and DA across the MA transporter and that in the used doses, the pressor effect of DA is mainly due to its indirect effect by releasing NE from sympathetic nerve terminals. Supported by funds from the American University of Beirut. Support or Funding Information Supported by funds from the American University of Beirut.