title: Regulation of catecholamine release in human adrenal chromaffin cells by β-adrenoceptors.
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 β(1)-, β(2)- and β(3)-adrenoceptors on catecholamine release from human adrenal chromaffin cells in culture. We observed that the β-adrenoceptor agonist (isoproterenol) and β(2)-adrenoceptor agonist (salbutamol) stimulated catecholamine (NE and EP) release from human adrenal chromaffin cells. Furthermore, the β(2)-adrenoceptor antagonist (ICI 118,551; 100 nM) and β(3)-adrenoceptor antagonist (SR 59230A; 100 nM) inhibited the catecholamine release stimulated by isoproterenol and nicotine in chromaffin cells. The β(1)-adrenoceptor antagonist (atenolol; 100 nM) 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 β(2)- and β(3)-adrenoceptors modulate the basal and evoked catecholamine release, NE and EP, via an autocrine positive feedback loop in human adrenal chromaffin cells.
authors.affiliation: CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Vera
authors.initials: V
authors.lastname: Cortez
authors.forename: Magda
authors.initials: M
authors.lastname: Santana
authors.forename: Ana Patrícia
authors.initials: AP
authors.lastname: Marques
authors.forename: Alfredo
authors.initials: A
authors.lastname: Mota
authors.forename: Joana
authors.initials: J
authors.lastname: Rosmaninho-Salgado
authors.forename: Cláudia
authors.initials: C
authors.lastname: Cavadas
mesh_terms: D001483:Base Sequence; D002395:Catecholamines / Q000378:metabolism*; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000378:metabolism*; D017931:DNA Primers; D006801:Humans; D016133:Polymerase Chain Reaction; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
chemical_list: D002395:Catecholamines; D017931:DNA Primers; D011943:Receptors, Adrenergic, beta