PAF-dependent phosphatidylinositol turnover in platelets: differences between asthmatics and normal individuals.
The effects of nebulized platelet-activating factor (PAF) on the pulmonary and cardiovascular systems, and on the platelets present in peripheral blood were investigated in 9 normal individuals and in 6 patients with asthma and 3 individuals with lyso-PAF. The inhalation of PAF caused an acute decrease in specific airway conductance. The circulatory system parameters monitored showed an increase in heart rate while blood pressure decreased in both groups that were studied. The inhalation of PAF led to a significant increase in the differential count of polymorphonuclear leukocytes after 15 min; the count returned to the initial level after 24 h. However, the platelet count remained unchanged. The phosphatidylinositol (PI) turnover and in particular the formation of 1,4,5-inositoltrisphosphate (IP3) in platelets were investigated after PAF inhalation. It also mediated an increase in intracellular free calcium concentration, [Ca2+]i, in response to a second challenge with exogenous PAF. The basal levels of IP3 and [Ca2+]i were significantly greater in the platelets of patients with asthma than in those of normal individuals (p less than 0.01). Platelets that had been isolated from normal and asthmatic subjects had a higher concentration of IP3 and [Ca2+]i in the platelets after an in vitro exposure to PAF. After an inhalation challenge with PAF, the platelets of both the normal individuals and the patients with asthma showed a specific refractoriness to the in vitro exposure to PAF. Perhaps, this is an explanation for the PAF-dependent tachyphylaxis that is commonly observed in both normal and asthmatic individuals.(ABSTRACT TRUNCATED AT 250 WORDS)
Block
L H
LH
Department of Medicine, University of Basel, Switzerland.
Imhof
E
E
Emmons
L R
LR
Roth
M
M
Perruchoud
A P
AP
D000208:Acute Disease; D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000097:blood* / Q000503:physiopathology; D001792:Blood Platelets / Q000378:metabolism*; D016084:Bronchoconstriction / Q000187:drug effects; D005260:Female; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000032:analysis / Q000096:biosynthesis; D008297:Male; D010716:Phosphatidylinositols / Q000032:analysis / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000494:pharmacology*; D010976:Platelet Count
D010716:Phosphatidylinositols; D010972:Platelet Activating Factor; D015544:Inositol 1,4,5-Trisphosphate