Technique for measurement of norepinephrine and 5-hydroxytryptamine uptake by rabbit lung.

Gillis, Chris; Iwasawa, Yasuo

doi:10.1152/jappl.1972.33.3.404

Cited by 56 publications

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“…Inhibition of both enzymes renders the system to a reversible site of loss, because uptake will then lead to amine accumulation within endothelial cells and net uptake will come to an end as soon as the rate of uptake equals the rate of efflux. This interpretation of our results is supported by in vitro studies carried out in the perfused rabbit lung (Gillis and Iwasawa 1972;Roth and Gillis 1975;Roth 1976, 1977). These studies show that in the isolated rabbit lung uptake of noradrenaline and dopamine goes hand in hand with the formation of deaminated and O-methylated metabolites, indicating the presence of both MAO and COMT activity.…”

Section: Discussionsupporting

confidence: 82%

The contribution by monoamine oxidase and catechol-O-methyltransferase to the total-body and pulmonary plasma clearance of catecholamines

Friedgen

Wölfel

Graefe

1996

Naunyn-Schmiedeberg's Arch Pharmacol

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To study the effects of inhibition of catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) on the removal of circulating catecholamines, anaesthetized rabbits were infused for 120 min with 3H-labelled noradrenaline, adrenaline and dopamine. Total-body plasma clearances (Cltot) and pulmonary fractional extractions (ERp) of the infused amines and the cardiac output of plasma (CO(p)) were determined under steady-state conditions at the end of each of two consecutive 60-min treatment periods. MAO and COMT were inhibited by treatment with pargyline (40 mg/kg) and tolcapone (3 mg/kg followed by 1.5 mg/kg given every 30 min), respectively. Two groups of animals were studied. Group I involved animals treated with tolcapone throughout and given pargyline at the beginning of the second treatment period. In group II, pargyline was given at the beginning of the first, and the treatment with tolcapone was started at the beginning of the second treatment period. As previous experiments had shown that COMT inhibition alone is without any effect on Cltot of the three catecholamines considered here, the results obtained in the first treatment period of group I can be taken to reflect control results. At the end of the first treatment period, Cltot of noradrenaline, adrenaline and dopamine (expressed as a percentage of CO(p)) was 88%, 85% and 142%, respectively, in group I (COMT inhibition) and 67%, 77% and 115%, respectively, in group II (MAO inhibition; P < 0.05 for the group difference regarding Cltot of noradrenaline and dopamine). MAO inhibition on top of COMT inhibition (group I) lowered Cltot of noradrenaline, adrenaline and dopamine by 23%, 12% and 26%, respectively, and COMT inhibition on top of MAO inhibition (group II) reduced Cltot of these catecholamines by 13%, 20% and 17%, respectively. At the end of the first treatment period, the pulmonary plasma clearance (Clp = ERp x CO(p)) of noradrenaline and dopamine was 13 and 25 ml kg-1 min-1, respectively, in group I and 12 and 28 ml kg-1 min-1, respectively, in group II. Clp of adrenaline did not differ from zero in either group. Clp of noradrenaline and dopamine was reduced by 74% and 70%, respectively, when both enzymes were inhibited in group I and by 70% and 67%, respectively, when both enzymes were inhibited in group II. Hence, inhibition of either MAO or COMT alone had little, if any, effect on the removal of noradrenaline, adrenaline and dopamine on passage through the systemic and pulmonary circulation. Combined inhibition of both MAO and COMT was highly effective in reducing the pulmonary clearance of noradrenaline and dopamine, but produced only minor decreases in the total-body clearance of all three catecholamines.

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Section: Discussionsupporting

confidence: 82%

The contribution by monoamine oxidase and catechol-O-methyltransferase to the total-body and pulmonary plasma clearance of catecholamines

Friedgen

Wölfel

Graefe

1996

Naunyn-Schmiedeberg's Arch Pharmacol

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“…It is possible, therefore, that hypoxia had acted on the metabolism of a variety of vasoconstrictor substances to prolong their effect. However, since pulmonary removal of serotonin (24,25) and norepinephrine (26,27) has been shown to be overwhelmed by microgram doses of these substances, the transport systems were most likely exhausted by the doses necessary to achieve marked pulmonary vasoconstriction. Furthermore, ouabain (1 mM) and cooling of the lungs, both of which have been shown to decrease pulmonary serotonin and norepinephrine removal (28)(29)(30) Shown are the Po2 of the venous blood draining the lung, the pulmonary arterial perfusion pressure just before injection of angiotensin II (base-line pressure), the maximal increase in pressure with angiotensin II injection (APap) and the vasodilation time (t = APap/2).…”

Section: Discussionmentioning

confidence: 99%

Hypoxia Impairs Vasodilation in the Lung

Voelkel¹,

McMurtry²,

Reeves³

1981

J. Clin. Invest.

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A B S T R A C T Alveolar hypoxia causes pulmonary vasoconstriction; we investigated whether hypoxia could also impair pulmonary vasodilation. We found in the isolated perfused rat lung a delay in vasodilation following agonist-induced vasoconstriction. The delay was not due to erythrocyte or plasma factors, or to alterations in base-line lung perfusion pressure. Pretreating lungs with arachidonic acid abolished hypoxic vasoconstriction, but did not influence the hypoxiainduced impairment of vasodilation after angiotensin II, bradykinin, or serotonin pressor responses. Progressive slowing of vasodilation followed angiotensin IIinduced constriction as the lung oxygen tension fell progressively below 60 Torr. KCI, which is not metabolized by the lung, caused vasoconstriction; the subsequent vasodilation time was delayed during hypoxia. However, catecholamine depletion in the lungs abolished this hypoxic vasodilation delay after KCIinduced vasoconstriction. In lungs from high altitude rats, the hypoxia-induced vasodilation impairment after an angiotensin II pressor response was markedly less than it was in lungs from low altitude rats. We conclude from these studies that (a) hypoxia impairs vasodilation of rat lung vessels following constriction induced by angiotensin II, serotonin, bradykinin, or KCI, (b) hypoxia slows vasodilation following KCIinduced vasoconstriction probably by altering lung handling of norepinephrine, (c) the effect of hypoxia on vasodilation is not dependent on its constricting effect on lung vessels, (d) high altitude acclimation moderates the effect of acute hypoxia on vasodilation, and (e) the hypoxic impairment of vasodilation is possibly the result of an altered rate of dissociation of agonists from their membrane receptors on the vascular smooth muscle.

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“…Transport of NA and 5-HT from the vascular space is considered to be the ratelimiting step in overall removal (Alabaster & Bakhle, 1970, 1973Junod, 1972;Gillis & Iwasawa, 1972 (Figure 2) and at least 75% on the average, of radioactivity in lung effluent is in the form of metabolite. Accordingly, removal in this case seems to reflect largely metabolic degradation.…”

Section: Discussionmentioning

confidence: 99%

“…After they leave the vascular space of perfused rabbit lung, 5-hydroxytryptamine (5-HT), noradrenaline (NA) and phenylethylamine are degraded by monoamine oxidase (MAO) and, in the case of NA, also by catechol-O-methyltransferase (COMT) (Hughes, Gillis & Bloom, 1969; Gillis & Iwasawa, 1972;Roth & Gillis, 1975). Three forms of MAO have been distinguished in the perfused lung.…”

Section: Introductionmentioning

confidence: 99%

The Fate of Biogenic Monoamines in Perfused Rabbit Lung

Gillis

Roth

1977

British J Pharmacology

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I Inactivation of f3-phenylethylamine and several of its derivatives was studied in a preparation of rabbit lung perfused with Krebs physiological medium at 370C. Inactivation or removal of these compounds was calculated as the difference between the concentration of each amine in the perfusion medium and the effluent, collected separately from each lung. The extent of amine metabolic degradation was also measured, by column chromatography, in lung effluent. 2 With this technique the magnitude of amine removal as a function of concentration was determined and an apparent Km and Vmax of removal were calculated for each amine. 3 Percentage removal was highest with phenylethylamine (95%), and decreased, apparently in relation to increasing phenyl-and side chain-hydroxylation (and therefore likely increased hydrophilicity), with 5-hydroxytryptamine (64%), tyramine (53%), octopamine (35%), dopamine (32%) and noradrenaline (23%). 4 Inactivation of each amine could be accounted for by metabolic degradation to deaminated products, which appeared in lung effluent within 90 s of beginning amine perfusion. 5 When intrapulmonary metabolism of phenylethylamine was inhibited by simultaneous perfusion with semicarbazide (10 mM) and pargyline (10 gM), the removal rate was unaltered, establishing that uptake of the amine from the vascular space is not dependent on metabolism at least for 4 min infusions.

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Technique for measurement of norepinephrine and 5-hydroxytryptamine uptake by rabbit lung.

Cited by 56 publications

References 0 publications

The contribution by monoamine oxidase and catechol-O-methyltransferase to the total-body and pulmonary plasma clearance of catecholamines

The contribution by monoamine oxidase and catechol-O-methyltransferase to the total-body and pulmonary plasma clearance of catecholamines

Hypoxia Impairs Vasodilation in the Lung

The Fate of Biogenic Monoamines in Perfused Rabbit Lung

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