Lithium preferentially inhibits adenylyl cyclase V and VII isoforms

作者：Mann Liad; Heldman Eliahu^*; Shaltiel Galit; Belmaker R H; Agam Galila

来源：International Journal of Neuropsychopharmacology, 2008, 11(4): 533-539.

DOI：10.1017/S1461145707008395

• Adenylyl cyclase
• dopamine
• isoforms
• lithium

Lithium ions' inhibition of adenylyl cyclase (AC) has not been previously Studied for the newly discovered AC isoforms. COS7 cells were transfected with each of the nine membrane-bound AC isoforms cDNAs with or without D(1)- or D(2)-dopamine receptor cDNA. AC activity was measured as [(3)H]cAMP accumulation in cells pre-incubated with [(3)H]adenine followed by incubation with phosphodiesterase inhibitors together with either the D, agonist SKF-82958 alone, or forskolin, in the presence or absence of the D(2) agonist quinpirole. At 1 mM or 2 mM lithium inhibited only AC-V activity when the enzyme was stimulated by forskolin, a direct activator of AC. Lithium inhibited AC-V (by 50%,), AC-VII (by 40%) and AC-II (by 25%) when Stimulated via the D(1) receptors, but did not affect the Ca(2+)-activated isoforms when stimulated by the Ca(2+) ionophore A23187. Quinpirole inhibits AC via the Gi protein. Lithium did not affect quinpirole-inhibited FSK-activated AC-V activity nor did it affect superactivated AC-V or AC-I following the removal of quinpirole. The data suggest interference of lithium with transduction pathways mediated via AC-V or AC-VII; only the active conformation of these AC isoforms is inhibited by lithium; the inhibitor), effect of lithium is abolished when the enzyme is superactivated. The marked inhibition of AC-V and AC-VII by lithium suggests that these two isoforms may be involved in mediating the mood-stabilizing effect of lithium.

• 出版日期2008-6
• 单位上海市精神卫生中心