The role of melatonin in pathogenesis of aspirin-sensitive asthma.
BACKGROUND
Platelets are involved in the pathogenesis of bronchial asthma, including aspirin-sensitive asthma (ASA). The pineal hormone melatonin (MT) has been described as inhibiting several physiological processes in platelets. The MT metabolite - N-acetyl-5-methoxy-kynurenamine - has a chemical structure similar to that of acetylsalicylic acid. Because ASA patients usually suffer from an active disease, despite the avoidance of aspirin and cross-reactive drugs, it has been suggested that the MT synthesis may be lower and sensitivity of platelet reception to MT may be higher in aspirin-sensitive asthmatic subjects than in aspirin-tolerant ones. The objective of this study was to investigate this hypothesis.


METHODS
We studied the urinary excretion of 6-sulphatoxymelatonin, the major metabolite of melatonin, and the effect of different MT doses on ADP-induced platelet aggregation in vitro in 17 ASA patients, 17 patients with aspirin-tolerant asthma (ATA) and 16 healthy subjects.


RESULTS
The results of the study have revealed a lower level of daytime aMT6s excretion in ASA patients (12.7 +/- 2.7 ng mL-1) than in ATA patients (32.7 +/- 9.9 ng mL-1, P < 0.05) and control subjects (19.9 +/- 5.8 ng mL-1, P < 0.05). The preincubation of platelet-rich plasma with the MT in a dose of 0.01 pg mL-1 plasma results in an increase in the intensity and the rate of the first platelet aggregation phase only in the ASA patients compared with the ATA patients and control subjects.


CONCLUSIONS
We conclude that the reduction in MT production in ASA patients defines the character of ADP-induced platelet aggregation and the change in its first phase after the further addition of MT in vitro. The latter is associated with the opening of some receptor-operated channels for Ca2+ or/and its mobilization from the intracellular stores. The higher sensitivity of platelet reception and a distorted reaction not only to MT but also to its metabolite may be prerequisites for aspirin intolerance in ASA patients.
Evsyukova
H V
HV
The I. P. Pavlov Medical University, St Petersburg, Russia. otd_ned@hotmail.com
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000293:Adolescent; D001241:Aspirin / Q000009:adverse effects*; D001249:Asthma / Q000097:blood / Q000139:chemically induced* / Q000503:physiopathology*; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002940:Circadian Rhythm; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008550:Melatonin / Q000031:analogs & derivatives* / Q000502:physiology* / Q000652:urine; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology; D012016:Reference Values
C054513:6-sulfatoxymelatonin; D000244:Adenosine Diphosphate; D008550:Melatonin; D001241:Aspirin