Normal serotonin uptake by blood platelets and brain synaptosomes but selective impairment of platelet serotonin storage in mice with Chediack-Higashi syndrome.
The Chediack-Higashi syndrome (CHS) is an autosomal recessive disorder reported in man and in several animal species including the "beige mice" (bg/bg). Among several manifestations of this genetic trait, deficiency of secretable substances - including serotonin - normally stored in platelet dense granules is a characteristic feature. The animal model of Chediak-Higashi syndrome used in the present study provides a unique opportunity to compare the kinetics of serotonin (5-hydroxytryptamine, 5-HT) uptake in platelets and brain synaptosomes in conditions of selective reduction of 5HT concentration in the platelets. The kinetics of 5HT uptake, as measured in the present study, was normal in synaptosomes and platelets from the same animals. The lower intraplatelet 5HT levels in bg/bg animals as compared to normal synaptosomes levels in the presence of normal uptake offer an indirect proof that the 5HT defect described in the CHS is due to an impaired 5HT storage mechanism. This is supported by the observation that spontaneous release of 5HT was markedly increased in platelets from CH5 mice but was normal in synaptosomes from the same animals. Thus platelets are a reliable model to study 5HT uptake, but not 5HT storage and release in brain synaptosomes.
M G
MG
Lampugnani
W
W
Buczko
A
A
Ceci
A
A
Mennini
G
G
de Gaetano
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002609:Chediak-Higashi Syndrome / Q000378:metabolism*; D005260:Female; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012701:Serotonin / Q000097:blood / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism*
D012701:Serotonin