Substance P receptor desensitization requires receptor activation but not phospholipase C

Previous studies have shown that exposure of parotid acinar cells to substance P at 37 degrees C results in activation of phospholipase C, formation of [3H]inositol 1,4,5-trisphosphate (IP3), and persistent desensitization of the substance P response. In cells treated with antimycin in medium containing glucose, ATP was decreased to approximately 20% of control values, IP3 formation was completely inhibited, but desensitization was unaffected. When cells were treated with antimycin in the absence of glucose, cellular ATP was decreased to approximately 5% of control values, and both IP3 formation and desensitization were blocked. A series of substance P-related peptides increased the formation of [3H]IP3 and induced desensitization of the substance P response with a similar rank order of potencies. The substance P antagonist, [D-Pro, D-Trp]-substance P, inhibited substance P-induced IP3 formation and desensitization but did not induce desensitization. These results suggest that the desensitization of substance P-induced IP3 formation requires agonist activation of a P-type substance P receptor, and that one or more cellular ATP-dependent processes are required for this reaction. However, activation of phospholipase C and the generation of inositol phosphates does not seem to be a prerequisite for desensitization.