Abstract
The possible age-related involvement of two different signal transduction pathways in the rat CNS was investigated. In the phosphytidyl inostiol (PI) response, higher phospholipase-C (PL-C) activity and drastically higher (almost 2.5-fold) inositol (1,4,5)trisphosphate (Ins(1,4,5) P(3)) concentration in the corpus striatum (caudate-putamen) of extremely old (approximately 40 months) female Wistar rats in comparison to young adult (approximately 3.5 months) rats were observed. In the adenosine 3':5'-cyclic monophosphate (cAMP) cascade, a significantly higher endogenus cAMP level and a significant decline of the adenylate cyclase (AC, ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1.) activity were observed in striatal tissue from young rats in comparison with aged rats. Binding saturation experiments with [(3)H]SCH 23390 at the dopamine (DA) D(1) receptor (D(1)) and [(3)H]spiperone at the DA D(2) receptor (D(2)) revealed no change in the affinity (K(d)) but a significant decrease in the density (B(max)) of D(1) (-31%, p<0.005) and of D(2) (-22%, p<0.05), respectively, in the aged versus young striata. DA seems to slightly inhibit total inositol phosphate formation and this effect was antagonized by (-)-sulpiride. A significant decrease (p<0.05) in the AC activity stimulated by 10 muM DA in the senescent compared to the young animals was monitored. Apparently, the age-related decline of the AC activity was independent of changes of G(S) and G(i) activity.
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