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Am J Physiol Cell Physiol 255: C149-C154, 1988;
0363-6143/88 $5.00
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AJP - Cell Physiology, Vol 255, Issue 2 C149-C154, Copyright © 1988 by American Physiological Society

ARTICLES

Substance P receptor desensitization requires receptor activation but not phospholipase C

H. Sugiya and J. W. Putney Jr
Section of Calcium Regulation, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.

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.


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