Correlation between inositol phospholipid hydrolysis and substance P receptors in rat CNS

Abstract

The undecapeptide substance P is a neurotransmitter candidate in the mammalian central and peripheral nervous system¹. Although the distribution of substance P-like immunoreactivity within the central nervous system (CNS) is well established², the recent identification and autoradiographic localization of specific substance P-binding sites has revealed numerous areas of mismatch between peptide levels and numbers of such sites^3–6. Previous studies have shown that substance P stimulates the hydrolysis of inositol phospholipids in peripheral tissues and in the hypothalamus^7,8, probably through stimulation of a polyphosphoinositide-specific phospholipase C (refs 9–11). Inositol phospholipid hydrolysis has been implicated in the mobilization of cytosolic calcium following receptor activation in several neurotransmitter and hormonal systems¹². We have therefore investigated the distribution of ³H-labelled substance P binding sites within various rat brain regions and correlated this with the rate of substance P-induced hydrolysis of inositol phospholipids in the same areas of the CNS. We found that the rate of inositol phospholipid hydrolysis was proportional to the number of binding sites specific for ³H-substance P, suggesting that binding sites revealed by ³H-substance P autoradiography correspond to functional substance P receptors.