Release of prostaglandins, a prostaglandin metabolite, slow-reacting substance and histamine from anaphylactic lungs, and its modification by catecholamines

Liebig, R.; Bernauer, W.; Peskar, Bernhard A.

doi:10.1007/bf00500347

Cited by 70 publications

(19 citation statements)

References 33 publications

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“…Bronchial smooth muscle relaxation results directly from 13-adrenoceptor stimulation, but the same receptor mechanism is also important in inhibiting the release of histamine, as shown by Schild (1), slowreacting substance of anaphylaxis, reported by Orange et al (2), and prostaglandins (Liebig, et al. [3]), presumably from mast cells in the lung parenchyma. For this reason, factors that impair this mechanism (for example injudicious use of nonselective p-blocking drugs) can have serious consequences in asthmatic patients.…”

Section: Introductionmentioning

confidence: 86%

The lymphocyte beta-adrenoceptor in normal subjects and patients with bronchial asthma: the effect of different forms of treatment on receptor function.

Conolly¹,

Greenacre²

1976

J. Clin. Invest.

203

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A B S T R A C T 83-adrenoceptor function has been compared in lymphocytes of normal subjects, asthmatic patients taking large doses of f3-adrenergic bronchodilators, and comparable asthmatics treated exclusively with nonadrenergic medication. The effect of prolonged administration of 8-adrenoceptor agonists on receptor function in normal subjects has also been examined. ,8-receptor response in each situation was quantitated by changes in levels of cyclic AMP, measured by a protein-binding assay.Dose response curves to isoproterenol (10 nM-0.1 mM) have been constructed for each group. Maximal increase in cyclic AMP in lymphocytes from normal subjects (393.2+44.0%) and in asthmatics on nonadrenergic preparations (408.3±46.7%) was significantly greater (P<0.001) than in asthmatics taking large doses of,8f-sympathomimetics (67.5±24.2%).Depression of the cyclic AMP response appeared to correlate with the degree of exposure to 13-adrenergic agonists but not with the prevailing severity of the patient's asthma.Withdrawal of 13-adrenergic drugs was followed by a reversion of the cyclic AMP response to normal values, which suggests that the depression was drug-induced rather than an inherent feature of the disease.This interpretation was confirmed by the finding that prolonged exposure of normal subjects to high doses of a,13-adrenergic agonist caused a marked and significant (P < 0.001) reduction in the cyclic AMP response, very similar to that seen in asthmatics on large doses of adrenergic bronchodilators.A possible link between drug-induced changes in the cyclic AMP response and the rise in the United Kingdom asthma death rate in the 1960's is discussed.

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Section: Introductionmentioning

confidence: 86%

The lymphocyte beta-adrenoceptor in normal subjects and patients with bronchial asthma: the effect of different forms of treatment on receptor function.

Conolly¹,

Greenacre²

1976

J. Clin. Invest.

203

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“…Most "releasing compounds" probably act by stimulating PG biosynthesis because PGs, TBXs, and prostacyclins are not stored in cells or tissues to any extent. One such "releasing" group is the catecholamines (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11). For example, the addition of NE to synaptosomes stimulates the production of the PG precursor arachidonic acid and other fatty acids (19).…”

Section: Resultsmentioning

confidence: 99%

“…Taken together, these results suggest that a-adrenergic receptor stimulation promotes the deacylation of phospholipids by MDCK cells whereas 0-adrenergic mechanisms lead to activation of similar pathways in WEHI-5 cells. The mechanism by which catecholamines stimulate the biosynthesis of prostaglandin-like substances in adipose tissue (1,2), spleen (3)(4)(5)(6), lungs (7), phrenic diaphragm (8,9), brain (10), kidney (11), and skin (2) is poorly understood. It is possible that these compounds stimulate via receptor-mediated mechanisms; for example, treatment with the a-adrenergic receptor blocking agent phenoxybenzamine inhibits the appearance of prostaglandin-like material from dog spleen (3,4,6) and rabbit kidney (11) after the administration of norepinephrine (NE).…”

mentioning

confidence: 99%

α- and β-adrenergic stimulation of arachidonic acid metabolism in cells in culture

Levine

Moskowitz

1979

Proc. Natl. Acad. Sci. U.S.A.

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Madin-Darby canine kidney cells (MDCK) synthesize prostaglandin (PG) F2, PGI2 (measured as 6-ketoPGEia), PGE2, PGD2, and thromboxane A2 (measured as thromboxane B2). When incubated in the presence of norepinephrine (6 p&M), the syntheses of these arachidonic acid metabolites are stimulated -fold. Norepinephrine's effect can be antagonized by the addition of a-adrenergic receptor blocking agents (phenoxybenzamine>phentolamine>yohimbine>di-benamine>tolazoline) but not by the 0-adrenergic blocking drugpropranolol. Norepinephrine's stimulation is also inhibited by low concentrations of dihydroergotamine, bromocryptine, ergocryptine, and ergotamine. The stimulation of PG synthesis by norepinephrine is reversible, continues during the 24 hr of incubation, and requires the presence of norepinephrine at the receptor site but it is not blocked by the addition of colchicine, cytochalasin B, or cycloheximide. Neither phenoxybenzamine nor ergotamine at concentrations that block norepinephrine's stimulation of PG biosynthesis suppresses the increase in PG synthesis induced by exogenous arachidonic acid, suggesting that the a-adrenergic regulation is not occurring primarily at the cyclooxygenase step in the metabolism of arachidonic acid.In mouse lymphoma cells (WEHI-5), low concentrations of isoproterenol or norepinephrine stimulate the synthesis of thromboxane, an effect that can be blocked by the addition of propranolol but not by relatively high concentrations of phenoxybenzamine or ergotamine. Taken together, these results suggest that a-adrenergic receptor stimulation promotes the deacylation of phospholipids by MDCK cells whereas 0-adrenergic mechanisms lead to activation of similar pathways in WEHI-5 cells. The mechanism by which catecholamines stimulate the biosynthesis of prostaglandin-like substances in adipose tissue (1, 2), spleen (3-6), lungs (7), phrenic diaphragm (8,9), brain (10), kidney (11), and skin (2) is poorly understood. It is possible that these compounds stimulate via receptor-mediated mechanisms; for example, treatment with the a-adrenergic receptor blocking agent phenoxybenzamine inhibits the appearance of prostaglandin-like material from dog spleen (3, 4, 6) and rabbit kidney (11) after the administration of norepinephrine (NE). It is also possible that prostaglandin-like substances are released as a result of tissue contraction (e.g., splenic capsule) induced by the catecholamines (6). On the other hand, stimulation of prostaglandin (PG) synthesis by the catecholami-nes may simply reflect their properties as cofactors for the cyclooxygenation of arachidonic acid, as shown by studies using microsomes prepared from seminal vesicles (12).In the present study, we examined the relationship between catecholamine receptors and PG synthesis by cells in culture.We now report that the regulation of PG biosynthesis is controlled, in part, by a-or f3-adrenergic receptors which, when stimulated, promote the deacylation of phospholipids and subsequent metabolism of arachidonic acid.MATERIALS AND MET...

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“…8-Adrenoceptor agonists have been shown to inhibit the non-histamine component of anaphylaxis in man and guinea-pig. Kaliner, Orange & Austen (1972) found that the release of slow reacting substance of anaphylaxis (SRS-A) from human lung fragments was inhibited by aadrenoceptor stimulants and similarly, Liebig, Bernauer & Peskar (1974) and Mathe & Levine (1973) reported a concomitant inhibition of histamine and prostaglandin F2a release from guinea-pig lung.…”

Section: Methodsmentioning

confidence: 91%

THE EFFECT OF CATECHOLAMINES ON THE in vivo AND in vitro RESPONSES OF THE CAT LUNG DURING ANAPHYLAXIS

Mitchell

Sparrow

1977

British J Pharmacology

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Anaphylaxis in the lung of cats actively sensitized to Ascaris antigen has been investigated in vivo and in vitro. In vivo there was a 100% increase in airways resistance and a 50% decrease in dynamic lung compliance following intravenous challenge with Ascaris antigen. Prostaglandin F2α induced similar changes but with histamine only dynamic lung compliance was affected. (‐)‐Isoprenaline prevented these prostaglandin F2α‐ and histamine‐induced changes and caused a delay of about 2 min in the onset of the mechanical changes following anaphylactic challenge. In vitro the isolated lung strip contracted within seconds of challenge whereas there was a delay of 2 to 3 min in the onset of the tracheal anaphylactic response. (‐)‐Isoprenaline, (‐)‐adrenaline and (+)‐noradrenaline reduced the magnitude of anaphylactic contractions of the isolated trachea but did not significantly affect those of the isolated lung strip. This indicated lack of inhibition of mediator release from the lung parenchyma. Histamine was released from sensitized lung fragments following challenge with the Ascaris extract. This release constituted 6.3% of the total tissue histamine and was not inhibited by (‐)‐isoprenaline (1 μM). (‐)‐Isoprenaline abolished 5‐hydroxytryptamine (5‐HT)‐induced contractions of the isolated trachea but not those elicited in response to acetylcholine. The isolated lung strip responses to histamine, prostaglandin F2α and 5‐HT were highly resistant to inhibition by (‐)‐isoprenaline.

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Release of prostaglandins, a prostaglandin metabolite, slow-reacting substance and histamine from anaphylactic lungs, and its modification by catecholamines

Cited by 70 publications

References 33 publications

The lymphocyte beta-adrenoceptor in normal subjects and patients with bronchial asthma: the effect of different forms of treatment on receptor function.

The lymphocyte beta-adrenoceptor in normal subjects and patients with bronchial asthma: the effect of different forms of treatment on receptor function.

α- and β-adrenergic stimulation of arachidonic acid metabolism in cells in culture

THE EFFECT OF CATECHOLAMINES ON THE in vivo AND in vitro RESPONSES OF THE CAT LUNG DURING ANAPHYLAXIS

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