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.
journal_name
Brain Resjournal_title
Brain researchauthors
Armstrong SM,Stuenkel ELdoi
10.1016/j.brainres.2005.02.040subject
Has Abstractpub_date
2005-05-10 00:00:00pages
76-86issue
1-2eissn
0006-8993issn
1872-6240pii
S0006-8993(05)00314-8journal_volume
1043pub_type
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