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Abstract: The adrenal gland plays a fundamental role in the response to a variety of stress situations. After a stress condition, adrenal medullary chromaffin cells release, by exocytosis, high quantities of catecholamine (epinephrine, EP; norepinephrine, NE), especially EP. Once in the blood stream, catecholamines reach different target organs, and induce their biological actions through the activation of different adrenoceptors. Adrenal gland cells may also be activated by catecholamines, through hormonal, paracrine and/or autocrine system. The presence of functional adrenoceptors on human adrenal medulla and their involvement on catecholamines secretion was not previously evaluated. In the present study we investigated the role of β1-, β2- and β3-adrenoceptors on catecholamine release from human adrenal chromaffin cells in culture. We observed that the β-adrenoceptor agonist (isoproterenol) and β2-adrenoceptor agonist (salbutamol) stimulated catecholamine (NE and EP) release from human adrenal chromaffin cells. Furthermore, the β2-adrenoceptor antagonist (ICI 118,551; 100nM) and β3-adrenoceptor antagonist (SR 59230A; 100nM) inhibited the catecholamine release stimulated by isoproterenol and nicotine in chromaffin cells. The β1-adrenoceptor antagonist (atenolol; 100nM) did not change the isoproterenol- neither the nicotine-evoked catecholamine release from human adrenal chromaffin cells. Moreover, our results show that the protein kinase A (PKA), protein kinase C (PKC), mitogen-activated protein kinase (MAPK) and phospholipase C (PLC) are intracellular mechanisms involved in the catecholamine release evoked by salbutamol. In conclusion, our data suggest that the activation of β2- and β3-adrenoceptors modulate the basal and evoked catecholamine release, NE and EP, via an autocrine positive feedback loop in human adrenal chromaffin cells. [Copyright &y& Elsevier]

The aim of the present work was to study the effect of angiotensin II (Ang II) on catecholamines and neuropeptide Y (NPY) release in primary cultures of human adrenal chromaffin cells. Ang II stimulates norepinephrine (NE), epinephrine (EP) and NPY release from perifused chromaffin cells by 3-, 2- and 12-fold, respectively. The NPY release is more sustained than that of catecholamines. We found that the receptor-AT2 agonist, T2-(Ang II 4–8)2 has no effect on NE, EP and NPY release from chromaffin cells. We further showed that Ang II increases intracellular Ca2+ concentration ([Ca2+]i). The selective AT1-receptor antagonist Candesartan blocked [Ca2+]i increase by Ang II, while T2-(Ang II 4–8)2 was ineffective. These findings demonstrate that AT1 stimulation induces catecholamine secretion from human adrenal chromaffin cells probably by raising cytosolic calcium. [Copyright &y& Elsevier]

Stress-induced increases in plasma epinephrine in man have been reported to decrease with age. To investigate the possible cellular basis for this decline we determined the characteristics of calcium currents and their relationship to catecholamine secretion in isolated human adrenal chromaffin (AC) cells. Cells derived from young individuals displayed prominent prepulse facilitation of L-type Ca channels but this property was absent in cells from older subjects. Robust quantal secretion in young cells as determined by amperometry was strongly coupled to the activation of these channels with an average delay of only ∼3 msec. N- and P-type Ca channels also contributed to secretion but were more weakly coupled to catecholamine release sites. Cells from older subjects secreted much less efficiently and showed only weak coupling between Ca channels and secretion. These studies suggest that the magnitude and timing of adrenal secretion changes with age and that the facilitation Ca channel is key to rapid activation of the fight-or-flight response in young individuals. [Copyright &y& Elsevier]