The quantal secretion of catecholamines is impaired by the accumulation of β-adrenoceptor antagonists into chromaffin cell vesicles

摘要: Background and purpose:  The delayed onset of certain effects antagonists β-adrenoceptors (β-blockers), such as lowering arterial blood pressure (several days), cannot be explained solely by their on β-adrenoceptors, an action that occurs within minutes. Although several mechanisms have been proposed, none them explain this temporal delay. This work aimed at providing a new explanation based the interference these drugs with functional accumulation catecholamines neurosecretory vesicles. Experimental approach:  We used simultaneous on-line monitoring catecholamine labetalol release from bovine isolated chromaffin cells rat perfused adrenal glands, well single cell amperometry, intracellular electrochemistry, patch amperometry HPLC. Key results:  Using three β-blockers, labetalol, atenolol propranolol, reduced quantal size secretory events in cells, accompanied slowing down exocytosis. By we found treatment β-blockers also increases vesicle volume, thereby creating dilution catecholamines. Experiments electrochemistry show vesicles uptake There was progressive β-blocker co-released tissues. Conclusions implications:  propose are progressively concentrated into sympathetic vesicles, interfere storage natural transmitters, resulting decrease tone. could hypotensive β-blockers.