[Analysis of the adverse effects of drugs at the cellular and subcellular levels].
A release of histamine after the lipophilic betablockers exaprolol and propranolol correlates with their capability of displacing the bound membrane Ca2+ and increasing the disorder of phospholipidic membranes of the isolated mast cells. Electron microscopy confirmed intracellular displacement of histamine from granules of mast cells after exaprolol without marked structural changes on the plasmatic membrane. Hydrophilic and selective atenolol, which does not possess a histamine-liberating effect, decreases spontaneous transfer of the intracellular calcium, decreases the disorder of the mast-cell membranes, and together with exaprolol and propranolol inhibits, in dose-dependence way, the gain of extracellular histamine in cells. The inhibitory effect of EDTA, tetrodotoxine and suramine on histamine release after exaprolol explains the non-receptor mechanism of exaprolol effect, which confirms a possibility of induction of adverse effects of blockers of the beta-adrenergic receptor in the development of a bronchospasm.
Ustav experimentálnej farmakológie Slovenskej akadémie vied, Bratislava.
R
R
Nosál'
K
K
Drábiková
J
J
Pecivová
K
K
Ondrias
J
J
Jakubovský
D000319:Adrenergic beta-Antagonists / Q000633:toxicity*; D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D002478:Cells, Cultured; D003593:Cytoplasm / Q000187:drug effects / Q000648:ultrastructure; D006636:Histamine Release / Q000187:drug effects; D010529:Peritoneal Cavity / Q000166:cytology; D010994:Pleura; D011412:Propanolamines / Q000633:toxicity*; D011433:Propranolol / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011433:Propranolol; C012969:exaprolol
Analýza neziadúcich úcinkov lieciv na bunkovej a subcelulárnej úrovni.