Role of the endoplasmic reticulum and mitochondria on quantal catecholamine release from chromaffin cells of control and hypertensive rats.
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.
Miranda-Ferreira
Regiane
R
Departamento de Farmacología, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
de Pascual
Ricardo
R
Caricati-Neto
Afonso
A
Gandía
Luis
L
Jurkiewicz
Aron
A
García
Antonio G
AG
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
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