Dopaminergic control over striatal targets appears to be retained in rats sustaining lesions of the nigrostriatal dopamine (DA) system as long as 5-10% of that projection remains. Similarly, during postnatal development, dopaminergic control over striatal neurons matures well before the innervation of striatum by the nigrostriatal bundle is attained. These observations suggest that enhanced efficacy of dopaminergic transmission may compensate for hypoinnervation of striatum after lesions or during development.To examine this hypothesis, striatal slices were superfused with Krebs bicarbonate buffer and effluent was collected and analyzed for endogenous DA. Electrical field stimulation (2 Hz) continuously delivered to slices prepared from intact adult rats increased DA efflux to 3-5 times the prestimulation rate within 10 min. Efflux then fell to approximately twice the basal rate over the next 20 min. DA efflux was also examined using slices prepared from adult animals given 6-hydroxydopamine 2-3 weeks earlier, and from 7-lo-d-old rat pups. In each group, striatal DA levels were 1 O-40% of adult control values. Nevertheless, stimulated DA efflux from these slices attained the same rate as that observed with intact, adult slices. Thus, fractional DA efflux from these slices was several times higher than the control rate by the end of the stimulation period. This increased DA efflux appeared to be a consequence of both increased release and decreased reuptake of DA, as the fractional DA efflux from control striatal slices could not be increased to the rate seen in hypoinnervated slices using nomifensine (10 PM), an inhibitor of DA efflux. Moreover, increased DA biosynthesis was indicated by the maintenance of DA stores in the hypoinnervated slices during stimulation.Thus, increased DA release, decreased reuptake, and increased synthesis may serve to compensate for hypoinnervation after injury or during development.The dopamine (DA)-containing neurons of the nigrostriatal bundle have significant influences on striatal function, as measured at both the cellular and behavioral levels (Ungerstedt, 197 1;Zigmond and Stricker, 1973;Marshall et al., 1974;

We compared the ability of the vasodilator prostaglandins PGI2, PGE2, and 13,14-dihydro PGE2 to release renin when infused into the denervated, nonfiltering canine kidney in vivo. Papaverine was used as a nonprostaglandin vasodilator. All the prostaglandins tested were capable of stimulating renin secretion, with the scale of potency being 13,14-dihydro PGE2 greater than PGI2 greater than PGE2; papaverine had no effect on renin secretion. These results indicate that both PGE2 and PGI2 can stimulate renin secretion but that vasodilation per se is not a stimulus. 13,14-Dihydro PGE2 was included because it is a poorer substrate than PGE2, both for transport into cells and catabolism to inactive products, but has comparable potency to PGE2 when tested in systems with limited ability to catabolize PGE2. The fact that 13,14-dihydro PGE2 was the most potent prostaglandin tested suggests that the effects of PGE2 in our system are reduced by the kidneys' recognized ability to extract and catabolize PGE2. Since PGI2 is less avidly metabolized than PGE2 by the kidney, the differences in observed potency between PGE2 and PGI2 could be largely the result of differences in renal catabolism of the two prostaglandins rather than differences in intrinsic potency. Therefore, both PGE2 and PGI2 are candidates for the endogenous prostaglandin responsible for stimulating renin secretion.