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.
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).
Rollandy
I
I
Laboratoire de biochimie des transports cellulaires, Université Paris XI, Orsay, France.
Dreux
C
C
Imhoff
V
V
Rossignol
B
B
D000818:Animals; D004789:Enzyme Activation; D066298:In Vitro Techniques; D007294:Inositol / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D008297:Male; D010306:Parotid Gland / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D010739:Phospholipase D / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013373:Substance P / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D010738:Type C Phospholipases / Q000378:metabolism
D007295:Inositol Phosphates; D010446:Peptide Fragments; D010716:Phosphatidylinositols; D013373:Substance P; D007294:Inositol; C032682:substance P (4-11); D010738:Type C Phospholipases; D010739:Phospholipase D