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.
Sugiya
H
H
Section of Calcium Regulation, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Putney
J W
JW
D000818:Animals; D000968:Antimycin A / Q000031:analogs & derivatives / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000378:metabolism; D007700:Kinetics; D008297:Male; D010306:Parotid Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D012016:Reference Values; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000378:metabolism*
D007295:Inositol Phosphates; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter; C032456:antimycin; D013373:Substance P; D000968:Antimycin A; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases