Amphetamine Stimulates Protein Kinase and Calcium Influx to Increase Corticosterone and Aldosterone Secretion from Male Rat Adrenal Cells

Ling-Ling Chang,Wan-Song Alfred Wun,Paulus S Wang,Cai-Yun Jian

doi:10.3844/ajptsp.2021.9.16

Ling-Ling Chang, Wan-Song Alfred Wun + Show 2 more

Open Access

https://doi.org/10.3844/ajptsp.2021.9.16

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Abstract

Amphetamine is a potent central nervous system stimulant. Clinical trials have demonstrated that in healthy adults, low (therapeutic) doses of amphetamine can improve i.e., cognition, memory, attention behavior. An amphetamine overdose can affect cardiovascular, central nervous system, musculoskeletal, respiratory, urinary, or sexual function. Furthermore, amphetamine can activate the hypothalamic-pituitary-adrenal axis to increase glucocorticoids and mineralocorticoids released from adrenal. The object of this research was to find out the effect of amphetamine in vivo and in vitro on the production of corticosterone and aldosterone by Zona Fasciculata-Reticularis (ZFR) cells and Zona Glomerulosa (ZG) cells from male rats. For the in vivo study, the rats were given intraperitoneal injections of saline (1 ml/kg/day, group 1), amphetamine (1 mg/ml/kg/day, group 2), or amphetamine (5 mg/ml/kg/day, group 3) for 7 days and then the ZFR or ZG cells from the sacrificed rats were incubated with other drugs. For the in vitro study, the adrenal cells of ZFR or ZG from untreated rats were incubated with amphetamine combined with other drugs. The corticosterone and aldosterone concentrations in samples of the medium were measured using radioimmunoassay. This in vitro and in vivo study illustrated that amphetamine can increase corticosterone secretion by ZFR cells and aldosterone secretion by ZG cells from male rats.

Highlights

Abuse of amphetamine-type Central Nervous System (CNS) stimulants is reaching an epidemic level around the world (United Nations Office on Drugs and Crime, 2010)
A23187, Adrenocorticotropic Hormone (ACTH, which increases the production and secretion of cortisol from the cortex of the adrenal gland), amphetamine, angiotensin II (AngII, which stimulates the secretion of aldosterone from the adrenal gland), Bovine Serum Albumin (BSA, a component of KRBGA medium), 8-Br-cyclic AMP (8-Br-cAMP, cAMP analog), Cyclopiazonic Acid (CPA, specific inhibitor of SERCA ATPase in intracellular Ca2+ storage sites), deoxycorticosterone, Forskolin (FSK, an adenylate cyclase agonist) and H89 were bought from Sigma Chemical Co
It could be that the ACTH- or forskolin-induced corticosterone arrived at the plateau level after Zona Fasciculata-Reticularis (ZFR) cells 4h incubation with ACTH or forskolin, which makes the effects of amphetamine disappeared

Summary

Introduction

Abuse of amphetamine-type Central Nervous System (CNS) stimulants is reaching an epidemic level around the world (United Nations Office on Drugs and Crime, 2010). Bazmi et al (2017) found that Iranian patients with cardiovascular complications were usually amphetamine abusers. Phupong and Darojn (2007) found that the pregnant abusing amphetamine experienced more obstetric symptoms than non-drug abusers. Berman et al (2008) found that amphetamine abuse causes brain structural abnormalities. In the medical dose range (e.g., in the treatment of obesity, attention deficit/hyperactivity disorder, or narcolepsy), amphetamine brings about mood and executive function changes, such as inducing good mood and the evolution of brain executive function. Very high-dose amphetamine causes damage to the dopamine system and nervous system in certain animals (Berman et al, 2008; Carvalho et al, 2012)

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