Hypothalamic substance P as a candidate for transmitter of primary afferent neurons

A peptide that exerts a depolarizing action on frog spinal motoneurons was found in the dorsal root of bovine spinal nerve. Pharmacological, chemical, and immunological properties of this motoneuron-depolarizing peptide were investigated and the results indicated that the peptide is identical with an undecapeptide, substance P, recently isolated from bovine hypothalamus by M.M. Chang and S.E.Leeman. The amount of hypothalamic substance P in bovine dorsal root determined by bioassay or radioimmunoassay was 24-130 pmole/g wet wt, whereas that in the ventral root was 9-27 times less. The effects of synthetic hypothalamic substance P on the isolated spinal cord of the frog and the newborn rat were studied. The peptide exerted a powerful depolarizing action on the motoneurons, its potency being about 200 times higher than that of L-glutamate. Distribution of substance P in the cat spinal cord was studied. The concentration of the peptide was highest in the dorsal part of dy lowered. When the dorsal root of the cat was ligated, substance P accumulated in a high concentration on the ganglion side of the ligature. These results, taken together, support the hypothesis that hypothalamic substance P is an excitatory transmitter of primary afferent neurons.