Active Uptake of Substance P Carboxy‐Terminal Heptapeptide (5–11) into Rat Brain and Rabbit Spinal Cord Slices

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Abstract
We previously reported that nerve terminals and glial cells lack an active uptake system capable of terminating transmitter action of substance P (SP). In the present study, we demonstrated the existence of an active uptake system for SP carboxy-terminal heptapeptide, (5–11)SP. When the slices from either rat brain or rabbit spinal cord were incubated with [3H](5–11)SP, the uptake of (5–11)SP into slices was observed. The uptake system has the properties of an active transport mechanism: it is dependent on temperature and sensitive to hypoosmotic treatment and is inhibited by ouabain and dinitrophenol (DNP). In the brain, (5–11)SP was accumulated by means of a high-affinity and a low-affinity uptake system. The Km and the Vmax values for the high-affinity system were 4.20 × 10−8m and 7.59 fmol/10 mg wet weight/min, respectively, whereas these values for the low-affinity system were 1.00 × 10−6m and 100 fmol/10 mg wet weight/min, respectively. In the spinal cord, there was only one uptake system, with a Km value of 2.16 × 10−7m and Vmax value of 26.2 fmol/10 mg wet weight/min. These results suggest that when SP is released from nerve terminals, it is hydrolysed into (5–11)SP before or after acting as a neurotransmitter, which is in turn accumulated into nerve terminals. Therefore, the uptake system may represent a possible mechanism for the inactivation of SP.