Pharmacological Regulation of the Late Steps of Exocytosis

• Published in: Annals of the New York Academy of Sciences Vol. 971; no. 1; pp. 184 - 192
• Main Authors: BORGES, RICARDO, MACHADO, J. DAVID, BETANCOR, GEMA, CAMACHO, MARCIAL
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.10.2002
• Subjects: 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester - pharmacology; Animals; calcium; Calcium - metabolism; Calcium Channel Agonists - pharmacology; cAMP; Cattle; cGMP; chromaffin cells; Chromaffin Cells - metabolism; Chromaffin Cells - physiology; Cyclic AMP - metabolism; Cyclic AMP-Dependent Protein Kinases - metabolism; Cyclic GMP - metabolism; Electrophysiology; Enzyme Activation; Exocytosis; Kinetics; Nitric Oxide - pharmacology; Protein Kinase C - metabolism; secretion; Signal Transduction
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1111/j.1749-6632.2002.tb04462.x

: We used amperometry to analyze the role of several second messengers and drugs in the exocytotic kinetics of bovine chromaffin cells. Activation of PKG produces a slowing down of exocytosis, which is not generally accompanied by changes in the net granule content of catecholamines. These effects are also observed after mild PKA activation. However, strong PKA stimulation also causes an increase in the apparent granule content of catecholamines, suggesting the presence of composed fusion. Conversely, PKC activation promotes acceleration of the exocytotic process. We also analyzed the contribution of different Ca2+ channel subtypes to the exocytotic kinetics at the single event level. Although N‐subtype channels do not contribute to total catecholamine release, their blockade produces a slowing down of exocytosis without changes in granule content. However, L or P/Q blockade causes, in addition, a reduction in the apparent granule content. The L‐type agonist BAY‐K‐8644 produces giant secretory amperometric spikes, indicating that Ca2+ favors composed fusion prior to exocytosis. Our data suggest that second messengers continuously regulate exocytotic kinetics and granule content. In addition, several well‐known antihypertensive agents, such as sodium nitroprusside, organic nitrates, hydralazine, or Ca2+ antagonists, could be acting through these novel mechanisms on sympathetic synapses by changing the synaptic performance, thereby producing additional vasodilatory effects.