title: Progesterone regulation of catecholamine secretion from chromaffin cells.
abstract: Stress stimulates the adrenal medulla to rapidly secrete catecholamines (CAs), and the adrenal cortex to release progesterone (PROG), which may locally regulate stress-induced CA release. We used bovine chromaffin cells to investigate the effects of PROG on CA secretion. PROG dose-dependently inhibited CA secretion induced by nicotinic acetylcholine receptor (nAChR) agonist 1,1-dimethyl-4-phenlypiperazinium iodide (DMPP) up to 77%. Pre-incubation with PROG up to 1 h increased this inhibition. 3alpha,5alpha-Tetrahydroprogesterone (3alpha,5alpha-THP) and dexamethasone were less potent inhibitors. Patch-clamp techniques revealed that PROG co-applied with DMPP inhibited peak DMPP-induced current up to 68% and with 3 min pre-incubation inhibited both peak and integrated current up to approximately 95%. Monitoring of FURA-2 showed that PROG similarly inhibited parallel changes in intracellular-free Ca(++) concentration. PROG also inhibited CA secretion elicited by elevated K(+) (38%), and, in single cells, suppressed Ca(++) current evoked by step depolarization, inhibiting amplitude by 15%, and reducing the time constant of current decay during depolarization by 57%. In contrast to the immediate inhibition of nicotinic current, inhibition of Ca(++) current became statistically significant only after 1 min exposure to PROG. PROG did not inhibit secretion stimulated by high Ca(++) perfusion of permeabilized cells. These data suggest that PROG inhibits CA secretion from chromaffin cells predominantly by rapidly inhibiting nAChRs, and by gradually enhancing the inactivation of voltage-dependent Ca(++) channels (VDCCs), but not by affecting secretory processes downstream of Ca(++) influx. This study supports a role for adrenocortical PROG in the regulation of CA secretion during stress.
authors.affiliation: Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109-0622, USA. siobhana@umich.edu
authors.forename: Siobhan M
authors.initials: SM
authors.lastname: Armstrong
authors.forename: Edward L
authors.initials: EL
authors.lastname: Stuenkel
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000502:physiology; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D018722:Nicotinic Agonists / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000502:physiology
chemical_list: D015220:Calcium Channels; D002395:Catecholamines; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D011374:Progesterone; D004246:Dimethylphenylpiperazinium Iodide; D002118:Calcium