Amphetamine enhances Ca2+ entry and catecholamine release via nicotinic receptor activation in bovine adrenal chromaffin cells.
Amphetamine, a psychostimulant, has been shown to act as a channel blocker of muscle nicotinic receptors and to induce a Ca(2+)-dependent secretion from adrenal chromaffin cells. In this study, the relationship between amphetamine and nicotinic receptors was studied using bovine adrenal chromaffin cells as a model system. Our results show that D-amphetamine sulfate alone induced an increase in the cytosolic Ca(2+) concentration ([Ca(2+)](c)) and [3H]norepinephrine release in a dose-dependent and extracellular Ca(2+)-dependent manner. Two common nicotinic receptor antagonists, hexamethonium and mecamylamine, suppressed the D-amphetamine sulfate-induced [Ca(2+)](c) rise and [3H]norepinephrine release. In addition, D-amphetamine sulfate inhibited the 1,1-dimethyl-4-phenyl-piperazinium iodide (DMPP)-induced [Ca(2+)](c) rise and [3H]norepinephrine release, but not the high K(+)- or veratridine-induced [Ca(2+)](c) increase and [3H]norepinephrine release. Antagonists, including alpha-bungarotoxin and choline, that are more specific for alpha7 nicotinic receptors were capable of inhibiting the D-amphetamine sulfate-induced [Ca(2+)](c) rise, while D-amphetamine sulfate was found to be capable of inhibiting the [Ca(2+)](c) rise induced by the alpha7-nicotinic receptor agonists, epibatidine and choline. Moreover, D-amphetamine sulfate dose-dependently suppressed [3H]nicotine binding to chromaffin cells. We, therefore, conclude that D-amphetamine sulfate acts as a nicotinic receptor agonist to induce [Ca(2+)](c) increase and [3H]norepinephrine release in bovine adrenal chromaffin cells.
Liu
Pei-Shan
PS
Department of Microbiology, Soochow University, Shihlin, Taipei, Taiwan, ROC. psliu@mail.scu.edu.tw
Liaw
Chwen-Tzy
CT
Lin
Meng-Kai
MK
Shin
Song-Huah
SH
Kao
Lung-Sen
LS
Lin
Lih-Fang
LF
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism*; D002413:Cations, Divalent / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D011978:Receptors, Nicotinic / Q000378:metabolism* / Q000502:physiology
D002395:Catecholamines; D002413:Cations, Divalent; D011978:Receptors, Nicotinic; D000661:Amphetamine; D002118:Calcium