Importance of the presence of the N-terminal tripeptide of substance P for the stimulation of phosphatidylinositol metabolism in rat parotid gland: a possible activation of phospholipases C and D

• Published in: Neuropeptides (Edinburgh) Vol. 13; no. 3; p. 175
• Main Authors: Rollandy, I, Dreux, C, Imhoff, V, Rossignol, B
• Format: Journal Article
• Language: English
• Published: Netherlands 01-04-1989
• Subjects: Animals; Enzyme Activation; In Vitro Techniques; Inositol - metabolism; Inositol Phosphates - metabolism; Male; Parotid Gland - metabolism; Peptide Fragments - pharmacology; Phosphatidylinositols - metabolism; Phospholipase D - metabolism; Rats; Rats, Inbred Strains; Structure-Activity Relationship; Substance P - metabolism; Substance P - pharmacology; Substance P - physiology; Type C Phospholipases - metabolism
• ISSN: 0143-4179
• DOI: 10.1016/0143-4179(89)90089-9

In this study, we have compared the effects of Substance P (SP) and an SP deprived of the N-terminal tripeptide, SP(4-11), on phosphoinositide metabolism by measuring phosphoinositide breakdown, inositol phosphate production and inositol incorporation into phosphoinositides. This work shows that SP and SP(4-11) have similar effects on phosphatidylinositol-4.5 bisphosphate (PIP2) metabolism. In fact, SP(4-11), like SP, induces a rapid PIP2 breakdown. On the contrary, SP and SP(4-11) have different effects on phosphatidylinositol (PI) metabolism since SP induces a decrease of radioactivity in PI, whereas SP(4-11) does not. Both peptides stimulate [3H]-inositol mono-, bis- and trisphosphate (respectively IP1, IP2, IP3) production in a time and dose-dependent manner. The kinetic of IP3 production is directly correlated with the one of PIP2 breakdown. The time course of IP1 production after SP(4-11) shows a time delay, while the one after SP does not. Since SP evokes an IP1 production without any delay and a large decrease of radioactivity in PI (which cannot account for the small amount measured in IP1 accumulation) we suggest that SP could activate a PI specific phospholipase C (leading to a PI breakdown) and a phospholipase D. These activations would require the complete structure of SP while the classical PIP2 specific phospholipase C activation (which induces PIP2 breakdown) would only require the carboxamide part of the peptide. So the complete structure of SP would be necessary to have a complete response (stimulation of PIP2 and PI metabolism).