Urinary N tau-methylimidazole acetic acid excretion in respiratory disease.
N tau-methylimidazole acetic acid (N tau-MIAA) is the principal urinary metabolite of histamine. The basal urinary excretion rate of N tau-MIAA was determined as 0.117 +/- 0.008 (SE) mg/h, with a renal clearance for N tau-MIAA of 273 +/- 27 ml/min implying active secretion. After subpharmacological infusion of histamine (50 ng.kg-1.min-1 over 2 h) in five volunteers that increased plasma histamine from 0.28 +/- 0.04 to 0.71 +/- 0.15 ng/ml, urinary excretion of N tau-MIAA over 8 h was increased by less than 17% compared with a control saline infusion. Urinary N tau-MIAA excretion in normal controls (273 +/- 14 micrograms/mmol creatinine) was similar to that observed in patients with severe acute asthma (253 +/- 22 micrograms/mmol), antigen-induced bronchoconstriction (269 +/- 21 micrograms/mmol), seasonal allergic rhinitis (304 +/- 31 micrograms/mmol), and clinically stable bronchiectasis (270 +/- 22 micrograms/mmol). In contrast, large increases in metabolite excretion (greater than 7,000 micrograms/mmol creatinine) were observed in a patient with systemic mastocytosis where very high plasma histamine levels were recorded (greater than 500 ng/ml) and marked systemic hemodynamic effects occurred. We conclude that urinary N tau-MIAA will only be increased in pathologies where sustained hyperhistaminemia occurs and that increased local histamine production in the lung or the upper airway does not cause a measurable change in the basal urinary excretion of this metabolite.
Taylor
I K
IK
Department of Clinical Pharmacology, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.
O'Malley
G
G
Murray
S
S
Turner
N
N
Taylor
G W
GW
Fuller
R W
RW
Pride
N
N
Dollery
C T
CT
D000328:Adult; D000941:Antigens / Q000008:administration & dosage; D005260:Female; D006632:Histamine / Q000097:blood; D006801:Humans; D007093:Imidazoles / Q000652:urine*; D008297:Male; D008407:Mast Cells / Q000502:physiology; D008875:Middle Aged; D012140:Respiratory Tract Diseases / Q000503:physiopathology / Q000652:urine*; D006255:Rhinitis, Allergic, Seasonal / Q000503:physiopathology / Q000652:urine
D000941:Antigens; D007093:Imidazoles; C002667:methylimidazoleacetic acid; D006632:Histamine