The effect of agents used in the treatment of bronchial asthma on carbohydrate metabolism and histamine sensitivity after beta-adrenergic blockade

Robert G. Townley, Dennis Daley, William Selenke

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Abstract

The common ability of theophylline and epinephrine to protect asthmatic patients against inhalation challenge, to protect mice sensitized to histamine by beta-adrenergic blockade, to produce hyperglycemia, and to alter the levels of liver and muscle glycogen has prompted a comparison of these effects with and without the prior administration of corticosteroids. In intact CFW mice epinephrine was protective against histamine and caused hyperglycemia. However, in adrenalectomized CFW mice epinephrine was neither protective against histamine nor did it cause hyperglycemia except when cortisone was administered. Contrawise, in CF1 mice even the combination of adrenalectomy and beta-adrenergic blockade with MJ-1999 (5 mg. per kilogram) fails to produce histamine sensitivity or prevent epinephrine hyperglycemia. However, liver glycogen is depleted in both strains of mice by epinephrine. In intact CFW mice under the experimental conditions employed, aminophylline induced glycogenolysis in liver but not in muscle in the presence of beta-adrenergic blockade. In fact, muscle glycogenesis increased with increasing doses of beta-adrenergic blockade in the presence of either aminophylline or epinephrine and correlated with the degree of histamine sensitivity. If another group of identically prepared mice are pretreated with hydrocortisone, there is restoration of the glycemic abnormality, increased liver glycogen, normalization of the muscle glycogen, and protection against histamine. These findings indicate that it is the increased peripheral uptake of glucose into glycogen rather than the level of glucose in the blood that more closely parallels sensitization to histamine challenge. The effect of corticosteroids in the adrenergically beta-blocked mouse reacting by themselves or enhancing the effect of theophylline or epinephrine may be interpreted in light of their effect on cyclic AMP by sensitizing the beta receptors, that is, lowering the receptor threshold to catecholamine action. It is postulated that corticosteroids work through a similar mechanism in bronchial asthma.

Original languageEnglish
Pages (from-to)87-91
Number of pages5
JournalJournal of Allergy
Volume45
Issue number2
DOIs
StatePublished - 1970

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Carbohydrate Metabolism
Adrenergic Agents
Histamine
Epinephrine
Asthma
Hyperglycemia
Liver Glycogen
Aminophylline
Muscles
Adrenal Cortex Hormones
Therapeutics
Theophylline
Glycogen
Sotalol
Glycogenolysis
Cortisone
Adrenalectomy
Cyclic AMP
Inhalation
Catecholamines

Cite this

The effect of agents used in the treatment of bronchial asthma on carbohydrate metabolism and histamine sensitivity after beta-adrenergic blockade. / Townley, Robert G.; Daley, Dennis; Selenke, William.

In: Journal of Allergy, Vol. 45, No. 2, 1970, p. 87-91.

Research output: Contribution to journalArticle

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