Further observation on the lack of active uptake system for substance P in the central nervous system.

Crude mitochondrial P2 fractions from bovine hypothalamus and substantia nigra, slices from rabbit spinal cord and mesencephalon and glial fractions from rabbit brain were incubated with [3H]-substance P and the uptake was measured and compared with those for 5-HT and GABA. Substance P was to some extent taken up into the fractions but this uptake was neither temperature nor time dependent and the pellet/medium ratios were less than 1. Similar results were obtained in high potassium treated slices from rabbit mesencephalon. The rate of uptake for [3H]-substance P increased linearly in proportion to the medium concentration, suggesting a non-saturable binding. These results, together with our previous observations provide strong evidence that nerve terminals and glial cells lack a temperature sensitive, active uptake system capable of terminating transmitter action of substance P at the synapse.