PT - JOURNAL ARTICLE AU - José D. Machado AU - Araceli Morales AU - José F. Gomez AU - Ricardo Borges TI - cAMP Modulates Exocytotic Kinetics and Increases Quantal Size in Chromaffin Cells DP - 2001 Sep 01 TA - Molecular Pharmacology PG - 514--520 VI - 60 IP - 3 4099 - http://molpharm.aspetjournals.org/content/60/3/514.short 4100 - http://molpharm.aspetjournals.org/content/60/3/514.full SO - Mol Pharmacol2001 Sep 01; 60 AB - The role of cAMP/cAMP-dependent protein kinase (PKA) on the late phase of exocytosis has been studied by amperometry on Ba2+-stimulated single bovine chromaffin cells. Forskolin (FSK) increases the intracellular cAMP levels in a concentration-dependent manner. Forskolin (100 nM) does not increase the number of exocytotic events, although it significantly increases the net granule content of catecholamines (CA), which is accompanied by a slowing of the process of degranulation. These effects are reversible, occur within 15 to 60 s, and are not due to newly synthesized CA. Isoprenaline, pituitary adenylate cyclase-activating polypeptide-38 or dB-cAMP reproduce FSK effects as does cholera toxin. The inhibition of phosphodiesterases with 3-isobutyl-1-methylxanthine mimics and potentiates the effect of FSK and isoprenaline. Rolipram and okadaic acid also produce a drastic increase in net granule content of CA, whereas H-89 attenuates the FSK response. These data indicate that cyclic AMP/PKA might favor the granule aggregation before its fusion with cell membrane and slow the late step of the exocytotic process. The American Society for Pharmacology and Experimental Therapeutics