Similar Effects of Substance P and Related Peptides on Salivation and on Phosphatidylinositol Turnover in Rat Salivary Glands

The effects of substance P and related peptides on salivation in vivo and on the incorporation of 3H-inositol into rat salivary gland lipids in vitro were compared. Physalaemin was the most active peptide tested on both responses. Substance P was less potent, but was three- to sixfold more potent than peptides consisting of the C-terminal 6-10 residues of substance P. Both the C-terminal pentapeptide and the C-terminal deamidated substance P showed a dramatic reduction of potency in both assays. Substance P receptors exist in all three rat salivary glands, and a stimulation of 3H-inositol incorporation was also observed in all three glands. The close correlation between the relative activities of the different substance P-related peptides in evoking salivation and 3H-inositol incorporation strongly indicates that the same population of substance P receptors is involved in each of these two responses and is consistent with the idea that phosphatidylinositol breakdown may be a reaction involved in stimulus-response coupling at the substance P receptors of salivary glands. The incorporation of 3H-inositol into parotid gland lipids could profitably be adopted as a simple and sensitive biochemical procedure for screening the biological activity of potential agonists and antagonists at substance P receptors.