The Fate of Biogenic Monoamines in Perfused Rabbit Lung

Gillis, Chris; Roth, Jerome A.

doi:10.1111/j.1476-5381.1977.tb07725.x

Cited by 35 publications

(26 citation statements)

References 10 publications

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“…On the other hand, PHE metabolism in the perfused lung has an apparent Km of 54 gIM which is very close to that measured in vitro. In rabbit isolated lung, PHE removal was anomalous in that alone out of six substrates the removal of this amine showed no saturation up to 830 gM, whereas 5-HT and noradrenaline in particular reached saturation at about 3 to 6 jiM (Gillis & Roth, 1977). The lack of effect of desmethylimipramine on PHE metabolism was unexpected for two reasons.…”

Section: Discussionmentioning

confidence: 97%

“…In rabbit isolated lung, PHE removal was anomalous in that alone out of six substrates the removal of this amine showed no saturation up to 830 gM, whereas 5-HT and noradrenaline in particular reached saturation at about 3 to 6 jiM (Gillis & Roth, 1977 (Alabaster & Bakhle, 1970;Junod, 1972a;Nicholas et al, 1974). We had therefore expected desmethylimipramine to decrease PHE metabolism, if not by inhibiting MAO, then at least by inhibiting uptake.…”

Section: Discussionmentioning

confidence: 99%

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THE METABOLISM OF 5‐HYDROXYTRYPTAMINE AND β‐PHENYL‐ETHYLAMINE IN PERFUSED RAT LUNG AND IN VITRO

Bakhle

Youdim

1979

British J Pharmacology

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1 Metabolism of 5-hydroxytryptamine (5-HT) and f,-phenylethylamine (PHE) by monoamine oxidase (MAO) was investigated in rat isolated lungs and in mitochondrial preparations from rat lung. 2 In perfused lungs 5-HT metabolism had an apparent Km of 2 gM and PHE metabolism a Km of 54 pIm, whereas in vitro the Km values were 330 gM and 28 gM respectively.3 In vitro, MAO activity had substrate and inhibitor specificities compatible with the presence of A and B types of MAO. 4 In perfused lung, metabolism of 5-HT but not that of PHE was inhibited by desmethylimipramine. 5 These results show that PHE metabolism in perfused lung, unlike that of other metabolized amines, is not limited by transport and the transport process for PHE is unlike that of 5-HT or noradrenaline. 6 These results also show that the kinetic parameters obtained for MAO activity in vitro do not generally apply to the isolated lung where transport of substrate can be the deciding factor. This discrepancy emphasizes that the enzymic properties of the whole organ cannot reliably be deduced from its enzymic content.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

THE METABOLISM OF 5‐HYDROXYTRYPTAMINE AND β‐PHENYL‐ETHYLAMINE IN PERFUSED RAT LUNG AND IN VITRO

Bakhle

Youdim

1979

British J Pharmacology

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“…MID methods applied to the lungs have the potential for discriminating among lungs having different physical and chemical properties such as occur in lung injury and disease (7,8,22,23,28,29,35). This is the basis for MID studies of lung water volume (8,12,21,28), capillary permeability (7,8,14,15,22,23,36,38), endothelial enzyme activity (8,9,15,18,29,35), and other aspects of lung tissue function (1-5, 7, 8, 16, 19, 20).…”

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confidence: 99%

Detection of changes in lung tissue properties with multiple-indicator dilution

Roerig

Audi²,

Linehan³

et al. 1999

Journal of Applied Physiology

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We evaluated the potential utility of a group of indicators, each of which targets a particular tissue property, as indicators in the multiple-indicator dilution method to detect and to identify abnormalities in lung tissue properties resulting from lung injury models. We measured the pulmonary venous outflow concentration vs. time curves of [14C]diazepam, 3HOH, [14C]phenylethylamine, and a vascular reference indicator following their bolus injection into the pulmonary artery of isolated perfused rabbit lungs under different experimental conditions, resulting in changes in the lung tissue composition. The conditions included granulomatous inflammation, induced by the intravenous injection of complete Freund's adjuvant (CFA), and intratracheal fluid instillation, each of which resulted in similar increases in lung wet weight. Each of these conditions resulted in a unique pattern among the concentration vs. time outflow curves of the indicators studied. The patterns were quantified by using mathematical models describing the pulmonary disposition of each of the indicators studied. A unique model parameter vector was obtained for each condition, demonstrating the ability to detect and to identify changes in lung tissue properties by using the appropriate group of indicators in the multiple-indicator dilution method. One change that was particularly interesting was a CFA-induced change in the disposition of diazepam, suggestive of a substantial increase in peripheral-type benzodiazepine receptors in the inflamed lungs.

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“…This was followed by distilled water (3 mL) and the eluates containing 5-HIAA were collected in pre-weighed glass vials. The adsorbed 5-HT was subsequently eluted with 0Á5 M hydrochloric acid (3 mL) into other pre-weighed glass vials (Gillis & Roth 1977). The vials were re-weighed and the volume of each eluate was determined.…”

Section: Experimental Protocolmentioning

confidence: 99%

The Effect of Fenfluramine on the Pulmonary Disposition of 5-Hydroxytryptamine in the Isolated Perfused Rat Lung: a Comparison with Chlorphentermine

Valodia

Syce

2000

Journal of Pharmacy and Pharmacology

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A possible mechanism for fenfluramine-induced pulmonary hypertension has been investigated. Fenfluramine, like chlorphentermine, may inhibit the pulmonary uptake and/or metabolism of 5-hydroxytryptamine (5-HT). This allows more 5-HT to remain in the pulmonary circulation, where it may exert a greater vasoconstrictor action resulting in pulmonary hypertension. Chlorphentermine has been shown to inhibit the uptake and metabolism of 5-HT. The effect of fenfluramine on the pulmonary disposition of [14C]5-HT has been investigated, in comparison with chlorphentermine, using a recirculating isolated perfused rat lung system. The pulmonary disposition of [14C]5-HT was assessed by measuring the change in [14C]5-HT concentration in the perfusion medium during the experiment and at the end, and the concentration in the lung at the end of the experiment. The concentration of 5-hydroxyindoleacetic acid, a metabolite of 5-HT, was measured in perfusate and lung samples. Mean pulmonary clearance of 5-HT for the control lung and lungs challenged with either fenfluramine (2.5 microM) or chlorphentermine (25 microM) was 4.514, 1.316 and 1.007 mL min(-1), respectively (n = 5). The concentration of 5-HT found in the lungs at the end of the experiment for the control and the lungs preloaded with fenfluramine or chlorphentermine was 695.05+/-9.69, 638.65+/-10.27 and 617.3+/-14.38 ng g(-1), respectively. Fenfluramine, like chlorphentermine, inhibited the pulmonary disposition of 5-HT resulting in an elevated perfusate level of 5-HT. This is a possible contributing mechanism for fenfluramine-induced pulmonary hypertension. The effect of fenfluramine was less pronounced than chlorphentermine.

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The Fate of Biogenic Monoamines in Perfused Rabbit Lung

Cited by 35 publications

References 10 publications

THE METABOLISM OF 5‐HYDROXYTRYPTAMINE AND β‐PHENYL‐ETHYLAMINE IN PERFUSED RAT LUNG AND IN VITRO

THE METABOLISM OF 5‐HYDROXYTRYPTAMINE AND β‐PHENYL‐ETHYLAMINE IN PERFUSED RAT LUNG AND IN VITRO

Detection of changes in lung tissue properties with multiple-indicator dilution

The Effect of Fenfluramine on the Pulmonary Disposition of 5-Hydroxytryptamine in the Isolated Perfused Rat Lung: a Comparison with Chlorphentermine

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