Release and metabolism of substance P in rat hypothalamus.

Abstract

THE isolation and characterisation of the undecapeptide substance P from extracts of central nervous tissue has promoted renewed interest in the function of this compound in the central nervous system (CNS)1. Tn addition, the development of a sensitive and specific radioimmuno-assay2 and complementary immunohistochemical techniques3 has provided evidence for a differential distribution of substance P in the CNS4,5. Application of substance P to the spinal cord of neonatal rats has been shown to produce a potent depolarising action on motoneurones6. Elsewhere in the CNS iontopheric application of substance P elicits a characteristic neuronal excitation which although slow in onset is long lasting7–10. If substance P is to be considered as a neurotransmitter in the CNS, demonstration of its release from nerve terminals in response to physiological depolarisation is the next essential prerequisite11. We have therefore studied the release of substance P from rat hypothalamus, and have demonstrated a potassium-evoked and calcium-dependent release of immunoreactive material. In addition preliminary results suggest that metabolic degradation rather than tissue uptake is responsible for the inactivation of substance P after its release from brain tissue.