title: Role of the endoplasmic reticulum and mitochondria on quantal catecholamine release from chromaffin cells of control and hypertensive rats.
abstract: Here, we present the first study on the effects of compounds that interfere with calcium (Ca(2+)) handling by the endoplasmic reticulum (ER) and mitochondria on amperometrically measured quantal catecholamine release from single adrenal chromaffin cells of control and spontaneously hypertensive rats (SHRs). Acetylcholine (ACh) or K(+) pulses triggered spike bursts of secretion by Ca(2+) entry through Ca(2+) channels. ER Ca(2+) release triggered by a mixture of caffeine, ryanodine, and thapsigargin (CRT) or carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) (a mitochondrial protonophore) also caused bursts of secretory spikes. The spike bursts generated by ACh, K(+), CRT, and FCCP were 3 to 4 times longer in SHRs compared with control cells; furthermore, the individual spikes were faster and had 3-fold greater quantal size. In additional experiments, a 90-s treatment was made with CRT or FCCP to block Ca(2+) handling by the ER and mitochondria. In these conditions, the integrated spike burst responses elicited by ACh and K(+) were potentiated 2- to 3-fold in control and SHR cells. This suggests that variations in Ca(2+) entry and its subsequent redistribution into the ER and mitochondria are not responsible for the greater secretion seen in SHRs compared with control cells; rather, such differences seem to be due to greater quantal content of spike bursts and to greater quantal size of individual amperometric events.
authors.affiliation: Departamento de Farmacología, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Regiane
authors.initials: R
authors.lastname: Miranda-Ferreira
authors.forename: Ricardo
authors.initials: R
authors.lastname: de Pascual
authors.forename: Afonso
authors.initials: A
authors.lastname: Caricati-Neto
authors.forename: Luis
authors.initials: L
authors.lastname: Gandía
authors.forename: Aron
authors.initials: A
authors.lastname: Jurkiewicz
authors.forename: Antonio G
authors.initials: AG
authors.lastname: García
mesh_terms: D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects; D020013:Calcium Signaling / Q000187:drug effects; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism*; D002469:Cell Separation; D019439:Chromaffin Cells / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D012433:Ryanodine / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D014475:Uncoupling Agents / Q000494:pharmacology
chemical_list: D002120:Calcium Channel Agonists; D015220:Calcium Channels; D002395:Catecholamines; D004791:Enzyme Inhibitors; D014475:Uncoupling Agents; D012433:Ryanodine; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D002110:Caffeine; D019284:Thapsigargin; D011188:Potassium; D002118:Calcium