PHARMACOLOGICAL ANALYSIS OF NOREPINEPHRINE AND 5-HYDROXYTRYPTAMINE REMOVAL FROM THE PULMONARY CIRCULATION: DIFFERENTIATION OF UPTAKE SITES FOR EACH AMINE

¹ Departments of Anesthesiology and Pharmacology, Yale University School of Medicine, New Haven, Connecticut

Removal of either norepinephrine (NE) or 5-hydroxytryptamine (5-HT), each at a concentration of 1.5 µM, from the vascular space of rabbit lung perfused in vitro, was significantly reduced by 10^-5 M cocaine, phenoxybenzamine, imipramine, and, to a lesser degree, by 10^-4 M normetanephnine. Aminophylline (10^-3 M) or phentolamine (10^-5 M) reduced removal of only NE (41, and 27%, respectively), while propranolol (10^-5 M) was ineffective as an inhibitor. Pretreatment of rabbits with 6-hydroxydopamine did not change pulmonary removal of NE or 5-HT, but significantly increased the vasoconstrictor response to infusion of either amine. Phenoxybenzamine blockade was irreversible: 45 minutes after establishment of the block, and despite perfusion during this time with phenoxyhenzamine-free Krebs' medium, removal of subsequently perfused 5-HT or NE (1.5 ,µM) was still inhibited. However, when 5-HT (10 µM) and phenoxybenzamine were perfused simultaneously and this was followed by a 45-minute perfusion with drug free medium, removal of 5-HT (1.5 µM) subsequently perfused was not blocked, while that of NE (1.5 µM) was inhibited. Accordingly, sites for NE and 5-HT transport into lung are separable pharmacologically.

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