PROTECTIVE EFFECT OF A NOVEL VINCA ALKALOID DERIVATIVE, VINCONATE, AGAINST ALTERATIONS IN BINDING-SITES OF 2ND MESSENGERS AFTER TRANSIENT CEREBRAL-ISCHEMIA IN GERBILS

1. We investigated the alterations in binding sites of three major second messengers, phorbol 12,13-dibutyrate, inositol 1,4,5-trisphosphate and forskolin following transient cerebral ischemia in gerbils, and examined the effects of a novel vinca alkaloid derivative, vinconate against the alterations in the binding of the second messengers following ischemia. 2. Transient cerebral ischemia produced by bilateral occlusion of the common carotid arteries was induced for 10 min, and intraperitoneal administration of vinconate (100 mg/kg and 300 mg/kg) was given 10 min before ischemia. 3. Morphological study indicated that transient ischemia can produce severe neuronal damage in striatum, hippocampal CA1 sector and hippocampal CA3 sector. 4. Transient cerebral ischemia caused the postischemic alterations in the binding of three second messengers. 5. The postischemic alterations in the binding of second messengers were ameliorated by pretreatment with vinconate. This effect was especially observed in the striatum which was most vulnerable to ischemia. 6. These findings are discussed in relation to the mechanism of ischemic neuronal damage.