Endogenous and pharmacological mechanisms for the regulation of human platelet cytosolic free Ca2+.
Because they inhibit the processes that promote elevation of [Ca2+]i and augment the processes that promote removal of Ca2+ from the cytosol, receptor antagonists, agents that mimic or elevate cAMP, cGMP or 1,2-Diacylglycerol (DG), and both inorganic and organic Ca2+ channel blockers can be considered to act as 'Ca2+ antagonists' on human platelets. Agonist-induced elevation of [Ca2+]i is associated with phosphoinositide hydrolysis. Unlike agents that mimic or elevate cAMP, cGMP or DG, receptor antagonists and organic Ca2+ influx, mobilisation of internal Ca2+ and inositol lipid hydrolysis. Lanthanides apparently inhibit only Ca2+ influx. Thus La3+ but not Verapamil or Diltiazem block receptor-operated Ca2+ channels on human platelets. The endogenous processes that promote extrusion or sequestration of cytosolic Ca2+ may be augmented by cAMP, cGMP, DG and by Ca2+. DG, via activation of protein kinase C, may serve as a bi-directional regulator of platelet reactivity.
D000634:Aminoquinolines; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000097:blood*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D004533:Egtazic Acid / Q000494:pharmacology; D005456:Fluorescent Dyes; D006706:Homeostasis; D006801:Humans; D007700:Kinetics; D010716:Phosphatidylinositols / Q000097:blood; D010972:Platelet Activating Factor / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011465:Prostaglandins, Synthetic / Q000494:pharmacology; D013931:Thromboxanes / Q000037:antagonists & inhibitors
D000634:Aminoquinolines; D002121:Calcium Channel Blockers; D005456:Fluorescent Dyes; D010716:Phosphatidylinositols; D010972:Platelet Activating Factor; D011450:Prostaglandin Endoperoxides, Synthetic; D011465:Prostaglandins, Synthetic; D013931:Thromboxanes; D004533:Egtazic Acid; C028429:U 44069; C034549:EP 045; C035739:Quin2; D002118:Calcium