Abstract
We previously described inhibition by racemic (±)-(1′R*,3R*)-3-phenyl-1 -[1′,2′,3′,4′-tetrahydro-5′,6′-methy l enedioxy-1′-napthalenyl-methyl]-pyrrolidine methanesulfonate (ABT-200), and its two constituent enantiomers, SS,ABT-200 and RR,ABT-200, of nicotine-stimulated but not histamine-stimulated catecholamine release from bovine adrenal chromaffin cells. To test the hypothesis that this inhibition reflects a blockade of Ca2+ influx, we used fura-2 loaded chromaffin cells to investigate cytosolic Ca2+ signals. We found that SS,ABT-200 inhibited nicotine- and K+-stimulated Ca2+ signals, both of which depend on Ca2+ influx. However, the early phase of the histamine-stimulated Ca2+ signals, which depends on Ca2+ mobilization from intracellular stores, was unaffected. We also examined ion flux through the nicotinic receptor by measuring 86rubidium+ (86Rb+) efflux from preloaded mouse midbrain synaptosomes. We found that SS,ABT-200 partially inhibited nicotine-stimulated 86Rb+ efflux, suggesting that it blocks ion flux through the nicotinic receptor directly. These data support a model in which ABT-200 blocks nicotine-stimulated catecholamine release by inhibiting cation flux through multiple channels.
Original language | English |
---|---|
Pages (from-to) | 177-182 |
Number of pages | 6 |
Journal | European Journal of Pharmacology: Molecular Pharmacology |
Volume | 269 |
Issue number | 2 |
DOIs | |
State | Published - Oct 14 1994 |
Bibliographical note
Funding Information:This work was supported by National Institutes of Mental Health predoctoral fellowship MH10316 to J.A.F., National Institutes of Health Grants AG00441 and AG06434 to G.A.G. and AA03527 and AG04418 to M.D.B.
Keywords
- Antidepressant
- Ca channel
- Catecholamine
- Chromaffin cell
- Histamine
- Nicotine
ASJC Scopus subject areas
- Pharmacology