Substance P receptor desensitization requires receptor activation but not phospholipase C
- National Institute of Environmental Health Sciences, Research Triangle Park, NC (USA)
Previous studies have shown that exposure of parotid acinar cells to substance P at 37{degree}C results in activation of phospholipase C, formation of ({sup 3}H)inositol 1,4,5-trisphosphate (IP{sub 3}), 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, IP{sub 3} 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 IP{sub 3} formation and desensitization were blocked. A series of substance P-related peptides increased the formation of ({sup 3}H)IP{sub 3} and induced desensitization of the substance P response with a similar rank order of potencies. The substance P antagonist, (D-Pro{sup 2}, D-Try{sup 7,9})-substance P, inhibited substance P-induced IP{sub 3} formation and desensitization but did not induce desensitization. These results suggest that the desensitization of substance P-induced IP{sub 3} 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.
- OSTI ID:
- 7007726
- Journal Information:
- American Journal of Physiology; (USA), Vol. 255:2; ISSN 0002-9513
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ANTIMYCIN
BIOLOGICAL EFFECTS
POLYPEPTIDES
BIOCHEMISTRY
RECEPTORS
CHEMICAL ACTIVATION
ATP
ENZYME INDUCTION
GLUCOSE
INOSITOL
LIPASES
SALIVARY GLANDS
TRITIUM COMPOUNDS
ALDEHYDES
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
BODY
CARBOHYDRATES
CARBOXYLESTERASES
CHEMISTRY
DRUGS
ENZYMES
ESTERASES
GENE REGULATION
GLANDS
HEXOSES
HYDROGEN COMPOUNDS
HYDROLASES
INOSITOLS
MEMBRANE PROTEINS
MONOSACCHARIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANS
PEPTIDES
PROTEINS
SACCHARIDES
551001* - Physiological Systems- Tracer Techniques