Effect of alpha 2-adrenoceptor blockade on lithium action in the rat brain.
The inhibitory effect of different concentrations of lithium (0.15-10 x 10(-3) M) on cAMP production induced by isoprenaline (1 x 10(-4) M) after the blockade of alpha(2)-adrenoceptors in the rat cerebral cortex was investigated. Low lithium concentrations (0.3-0.6 x 10(-3) M) exerted a significant inhibitory effect after yohimbine (1 x 10(-5) M) addition, but had no effect when isoprenaline alone or prazosin (1 x 10(-7) M) was added. The recovery of [3H]yohimbine binding after irreversible inactivation by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) was evaluated in cortical membranes to study how alpha(2)-adrenoceptor repopulation affects the action of lithium on the adenylyl cyclase-cAMP system. When the density of alpha(2)-adrenoceptors was lower than 21%, lithium showed a significant inhibitory effect at all concentrations tested. However, at higher densities, increased concentrations of lithium were required to inhibit cAMP production. Our results suggest that the inhibitory effect of lithium on cAMP levels in the rat brain is conditioned by alpha(2D)-adrenoceptors.
Laura Cuffi
M
M
Department of Pharmacology and Medicinal Chemistry, School of Medicine, University of Barcelona, Casanova 143, 08036 Barcelona, Spain. cuffi@medicina.ub.es
Carbonell
Lourdes
L
Mármol
Frederic
F
Giménez
José
J
Forn
Javier
J
D018674:Adrenergic Antagonists / Q000378:metabolism / Q000494:pharmacology*; D058669:Adrenergic alpha-2 Receptor Antagonists; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018021:Lithium Chloride / Q000494:pharmacology*; D008297:Male; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism / Q000502:physiology*
D018674:Adrenergic Antagonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D018341:Receptors, Adrenergic, alpha-2; D000242:Cyclic AMP; D018021:Lithium Chloride