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The action of pentobarbitone on stimulus‐secretion coupling in adrenal chromaffin cells
Author(s) -
Pocock G.,
Richards C.D.
Publication year - 1987
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1987.tb16826.x
Subject(s) - carbachol , catecholamine , calcium , depolarization , secretion , chemistry , exocytosis , extracellular , endocrinology , medicine , adrenal medulla , acetylcholine , chromaffin cell , calcium in biology , biophysics , biology , biochemistry , stimulation
1 The action of pentobarbitone on stimulus‐secretion coupling was studied in bovine isolated adrenal medullary cells. 2 Pentobarbitone inhibited catecholamine release evoked by 500 μ m carbachol with half maximal inhibition (IC 50 ) around 50 μ m . It also inhibited catecholamine release induced by depolarization with 77 m m potassium (IC 50 100 μ m ). These effects of pentobarbitone were observed with concentrations that lie within the range encountered during general anaesthesia. 3 Evoked secretion required the presence of calcium in the extracellular medium and was associated with an influx of Ca 2+ through voltage‐sensitive channels. Pentobarbitone inhibited 45 Ca influx in response to both carbachol (IC 50 50 μ m ) and K + ‐depolarization (IC 50 150 μ m ). 4 The action of pentobarbitone on the relationship between intracellular free Ca and exocytosis was examined using electropermeabilised cells which were suspended in solutions containing a range of concentrations of ionised calcium between 10 −8 and 10 −4 M. Catecholamine secretion was measured in the presence of 0, 50, 200 or 500 μ m pentobarbitone. The anaesthetic had no effect on the activation of exocytosis by intracellular free calcium. 5 When catecholamine secretion in response to potassium or carbachol was modulated by varying extracellular calcium or by adding pentobarbitone to the incubation medium, the amount of catecholamine secretion for a given Ca 2+ entry was the same. 6 Pentobarbitone inhibited the secretion and 45 Ca uptake induced by carbachol in a non‐competitive manner. 7 The secretion evoked by nicotinic agonists was associated with an increase in 22 Na influx. Pentobarbitone inhibited this influx with an IC 50 of 100 μ m . 8 We concluded that: (a) Pentobarbitone inhibits the catecholamine secretion from bovine adrenal chromaffin cells induced by nicotinic agonists by non‐competitive inhibition of the nicotinic receptor. (b) The decrease in Ca influx caused by pentobarbitone accounts fully for the decrease in secretion in response to depolarization with potassium.