Histamine metabolism in bronchial asthma

Kerr, James W (1968) Histamine metabolism in bronchial asthma. MD thesis, University of Glasgow.

Abstract

This thesis is a study of the metabolism of endogenous and exogenous histamine in patients with bronchial asthma and control subjects. The effect of exogenous histamine on pulmonary ventilation in these subjects is also investigated. A preliminary experiment in part I confirms) observations already published by Dr. R. W. Schayer in which the urinary metabolites of C14 histamine injected into guinea pigs are identified by paper chromatography and autoradiography. The principal metabolites are C14 1-methyl, 4-imidazole acetic acid,C14 l1ribosyl imidazole acetic acid and C14 1-methyl histamine. The methods used in this preliminary experiment were developed and used to examine the urine extracts of patients admitted to hospital in status asthmaticus for the naturally occurring metabolites of histamine. The effect of treatment with corticotrophin gel on the urinary metabolites of histamine is also reported. Urine extracts from non allergic subjects were examined as controls. Patients admitted in status asthmaticus were found to have the imidazole, urocanic acid in their urine extracts and no evidence of histamine or of the principal metabolite of histamine in man, 1-methyl, 4-imidazole acetic acid, or of the alternative metabolite 1-ribosyl imidazole acetic acid. In contrast the urine extracts of controls contained no urocanic acid and the histamine metabolite 1-methyl, 4-imidazole acetic acid was identified in significant quantity. Within 24 hours of starting corticotrophin treatment in the asthmatic subjects, the urocanin acid had disappeared and 1-methyl, 4 imidazole acetic acid could be identified in the urine extracts. Histamine itself was also identified in the urine extracts of half of the asthmatic subjects studied whilst on corticotrophin. The significance of the observations in Part I is discussed and it is being suggested that in an attack of asthma histamine is being retained in the body and not made available for metabolism. This leads to a feed back via 1-histidine and overloading the metabolic pathway from l-histidine via urocanic acid to glutamic acid. The effect of corticotrophin gel to release endogenous histamine and its metabolite 1-methyl, 4-imidazole acetic acid appears in the urine. At the same time urocanic acid disappears from the urine (see attached figure). Part II is a comparison of the metabolism of infused C14 histamine dihydrochloride in asthmatic subjects with that in controls. The levels of radioactivity in the urine and serum of the two groups are compared in the 24 hours after the infusion and there is shown to be no significant difference in the two groups. The urinary and serum metabolites of C14 1-methyl, 4-imidazole acetic acid and C14 1-ribosyl, 4-imidazole acetic acid and again there is shown to be no significant difference in the rate of metabolism or in the metabolic pathway of C14 histamine in the two groups. During the infusion of C14 histamine there was diminished pulmonary ventilation in the asthmatic subjects as compared to the controls and this is shown to be statistically significant. This well known hyper-sensitivity of ventilation in asthmatic subjects to histamine is discussed in relationship to this study and to the recently proposed hypothesis that histamine super-sensitivity is due to a disturbed function of the alpha and beta receptors on bronchial smooth muscle. Finally preliminary results are reported to show that alpha adrenergic receptor blocking drugs can alter histamine supersensitivity and inhibit the fall in ventilation in asthmatic subjects which follows an infusion of histamine.

• Item Type: Thesis (MD)
• Qualification Level: Doctoral
• Additional Information: Advisers: J Reid; B Bonte-Stewart
• Keywords: Physiology
• Date of Award: 1968
• Depositing User: Enlighten Team
• Unique ID: glathesis:1968-72767
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 11 Jun 2019 11:06
• Last Modified: 11 Jun 2019 11:06
• URI: https://theses.gla.ac.uk/id/eprint/72767