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The effect of nitric oxide on blockade of the norepinephrine transporter, uptake‐1, by imipramine
Author(s) -
Simaan Joseph A.
Publication year - 2012
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.26.1_supplement.844.3
Subject(s) - methoxamine , nitric oxide , blockade , chemistry , imipramine , tyramine , norepinephrine , pharmacology , medicine , endocrinology , agonist , receptor , biochemistry , alternative medicine , organic chemistry , pathology , dopamine
In a previous study (Eur. J. Pharmacol, 2011) we showed that fresh synthesis of nitric oxide (NO) modulates transport of norepinephrine (NE) and tyramine (T) by uptake‐1 and its blockade by cocaine. We explored the effect of blocking the synthesis of NO with Nw‐nitro‐L‐arginine (L‐NNA) and restoration of the rise in pressure it induces with nitroglycerin, a nitric oxide donor (NG), on blockade of uptake‐1 by imipramine (IM), tested by modulation of the pressor responses of sympathomimetic amines that act directly like NE, that release NE like T, and which spare uptake‐1 like methoxamine (M), in anesthetized Sprague‐Dawley rats with measurement of mean arterial pressure. IM reduced the pressor effect of T by 81–85% which was restored after L‐NNA/NG by 233–641% (P<0.000) in different doses (0.025–0.1 mg). IM potentiated the pressor effect of NE by 60–86% (P<0.000), and decreased the pressor effect of M minimally with no further change after L‐NNA/NG. L‐NNA/NG relieved blockade of uptake‐1 and restored the pressor effect of T without further effect on NE because of opposing actions, relief of IM effect and direct depression of entry of NE. Minimal depression of the pressor effect of methoxamine is due to the alpha‐adrenoceptor blockade of IM. It is concluded that fresh synthesis of nitric oxide is significantly involved in the blocking activity of IM on uptake‐1. Supported by the American University of Beirut.