5-Hydroxytryptamine (5-HT)-induced shape change in human platelets determined by computerized data acquisition: correlation with [125I]-iodoLSD binding at 5-HT2 receptors.
The 5-HT-induced shape change and subsequent aggregation of platelets provides a functional assay for 5-HT2 receptors. In the present study we describe a method to increase aggregometer sensitivity by digital conversion of the voltage produced by changes in light transmittance through a platelet suspension, thereby allowing accurate analyses of the primary shape-change response. The pharmacology of 5-HT-induced shape change was then compared with that of [125I]-iodoLSD binding in human platelets. 5-HT caused a dose-dependent change in platelet shape (maximum response 5 x 10(-6) M, EC50 10(-6) M). Furthermore, there was a significant correlation across a selection of drugs between IC50 values for inhibition of 5-HT-induced shape change and for inhibition of platelet binding of the 5-HT2 receptor ligand [125I]-iodoLSD. These results support the hypothesis that 5-HT-induced shape change and [125I]-iodoLSD binding in human platelets are mediated through the same receptor, and validate the methods of data acquisition described.
Brazell
C
C
Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, UK.
McClue
S J
SJ
Preston
G C
GC
King
B
B
Stahl
S M
SM
D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D008238:Lysergic Acid Diethylamide / Q000031:analogs & derivatives* / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; C039496:2-iodolysergic acid diethylamide; D008238:Lysergic Acid Diethylamide