Membrane bilayer balance and platelet shape: morphological and biochemical responses to amphipathic compounds.
Activated platelets adopt a characteristic spiculate morphology. A wide variety of anionic and zwitterionic amphipathic compounds were found to effect a similar shape change and to cause the open canalicular system to become less prominent. Several cationic amphipaths reversed thrombin-, PAF-, and amphipath-induced spiculation and restored the discoid shape. Higher concentrations of cationic amphipaths caused the cells to assume spheroid and indented forms, and caused the canalicular system to appear more prominent. Three amphipaths were studied further to address possible mechanisms underlying their morphological effects. Dilauroylphosphatidylcholine was found to induce spiculation without causing the changes in protein phosphorylation and inositide metabolism generally associated with platelet activation. Two other amphipaths, chlorpromazine (which induced sphering) and dilauroylphosphatidylserine (which caused spiculation followed by sphering) caused specific changes in protein and/or lipid phosphorylation, which may be responsible for some, but not all, of the morphological effects of these compounds. To account for these findings, we propose that platelet shape can be influenced by changes in the plasma membrane bilayer balance. Agents that bind to the membrane outer monolayer are accommodated by spiculation; those that bind to the inner monolayer are accommodated by sphering.
Ferrell
J E
JE
Department of Chemistry, Stanford University, CA 94305.
Mitchell
K T
KT
Huestis
W H
WH
D000328:Adult; D000838:Anions; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D002412:Cations; D002462:Cell Membrane / Q000378:metabolism; D002746:Chlorpromazine / Q000494:pharmacology; D003992:Dibucaine / Q000494:pharmacology; D004134:Dimyristoylphosphatidylcholine / Q000494:pharmacology; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects; D006801:Humans; D008051:Lipid Bilayers / Q000378:metabolism*; D008563:Membrane Lipids / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D010712:Phosphatidic Acids / Q000494:pharmacology*; D010713:Phosphatidylcholines / Q000494:pharmacology; D010718:Phosphatidylserines / Q000494:pharmacology; D010766:Phosphorylation; D010972:Platelet Activating Factor / Q000494:pharmacology; D013748:Tetracaine / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology
D000838:Anions; D002412:Cations; D008051:Lipid Bilayers; D008563:Membrane Lipids; D008565:Membrane Proteins; D010712:Phosphatidic Acids; D010713:Phosphatidylcholines; D010718:Phosphatidylserines; D010972:Platelet Activating Factor; D013748:Tetracaine; C015153:1,2-dilauroylphosphatidylcholine; C055534:dilauroylphosphatidylserine; D013917:Thrombin; D003992:Dibucaine; D002746:Chlorpromazine; D004134:Dimyristoylphosphatidylcholine