Inhibition of /sup 22/Na influx by tricyclic and tetracyclic antidepressants and binding of (/sup 3/H)imipramine in bovine adrenal medullary cells
In bovine adrenal medullary cells we investigated the effects of antidepressants on ionic channels and secretion of catecholamines. Tricyclic (imipramine, amitriptyline and nortriptyline) and tetracyclic (maprotiline and mianserin) antidepressants inhibited carbachol-induced influx of /sup 22/Na, /sup 45/Ca and secretion of catecholamines (IC50, 14-96 microM). Influx of /sup 22/Na, /sup 45/Ca and secretion of catecholamines due to veratridine also were inhibited by these drugs (IC50, 10-17 microM). However, antidepressants did not suppress high concentration of K-induced 45Ca influx and catecholamine secretion, suggesting that antidepressants do not inhibit voltage-dependent Ca channels. (/sup 3/H)Imipramine bound specifically to adrenal medullary cells. Binding was saturable, reversible and with two different equilibrium dissociation constants (13.3 and 165.0 microM). Tricyclic and tetracyclic antidepressants competed for the specific binding of (/sup 3/H)imipramine at the same concentrations as they inhibited /sup 22/Na influx caused by carbachol or veratridine. Carbachol, d-tubocurarine, hexamethonium, tetrodotoxin, veratridine and scorpion venom did not inhibit the specific binding of (/sup 3/H)imipramine. These results suggest that tricyclic and tetracyclic antidepressants bind to two populations of binding sites which are functionally associated with nicotinic receptor-associated ionic channels and with voltage-dependent Na channels, and inhibit Na influx. Inhibition of Na influx leads to the reduction of Ca influx and catecholamine secretion caused by carbachol or veratridine.
- Research Organization:
- Univ. of Occupational and Environmental Health, Kitakyushu, Japan
- OSTI ID:
- 5786239
- Journal Information:
- J. Pharmacol. Exp. Ther.; (United States), Vol. 243:1
- Country of Publication:
- United States
- Language:
- English
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ANTIDEPRESSANTS
BIOLOGICAL EFFECTS
CALCIUM
MEMBRANE TRANSPORT
CATECHOLAMINES
SECRETION
SODIUM
BIOCHEMICAL REACTION KINETICS
BRAIN
CALCIUM 45
CATTLE
IMIPRAMINE
INHIBITION
NERVE CELLS
RECEPTORS
SODIUM 22
STRUCTURE-ACTIVITY RELATIONSHIPS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ALKALI METAL ISOTOPES
ALKALI METALS
ALKALINE EARTH ISOTOPES
ALKALINE EARTH METALS
AMINES
ANIMAL CELLS
ANIMALS
AROMATICS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
BODY
CALCIUM ISOTOPES
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM AGENTS
DAYS LIVING RADIOISOTOPES
DOMESTIC ANIMALS
DRUGS
ELEMENTS
EVEN-ODD NUCLEI
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
INTERMEDIATE MASS NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LABELLED COMPOUNDS
LIGHT NUCLEI
MAMMALS
MEMBRANE PROTEINS
METALS
NERVOUS SYSTEM
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PHENOLS
POLYPHENOLS
PROTEINS
PSYCHOTROPIC DRUGS
RADIOISOTOPES
REACTION KINETICS
RUMINANTS
SODIUM ISOTOPES
SOMATIC CELLS
VERTEBRATES
YEARS LIVING RADIOISOTOPES
550201* - Biochemistry- Tracer Techniques