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Text
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URL Address
<a href="http://doi.org/10.1124/jpet.104.079954" target="_blank" rel="noreferrer noopener">http://doi.org/10.1124/jpet.104.079954</a>
Pages
1347–1354
Issue
3
Volume
313
Dublin Core
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Title
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Neurokinin-1 receptor resensitization precedes receptor recycling.
Publisher
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The Journal of pharmacology and experimental therapeutics
Date
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2005
2005-06
Subject
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Adenosine Triphosphate/pharmacology; Animals; Binding; Calcium/metabolism; CHO Cells; Competitive; Cricetinae; Guanylyl Imidodiphosphate/pharmacology; Neurokinin-1/*metabolism; Phosphorylation; Rats; Receptors; Substance P/metabolism
Creator
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Bennett V J; Perrine S A; Simmons M A
Description
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Following agonist binding, neurokinin-1 receptors undergo rapid desensitization followed by internalization and recycling. Desensitization requires receptor phosphorylation but does not require internalization, whereas resensitization is thought to require internalization and recycling. Our previous data, however, have suggested that, following activation and desensitization, the return of responsiveness to the neurokinin-1 agonist substance P (termed "resensitization") occurs hours before internalized receptors are recycled back to the plasma membrane. To further investigate this novel mechanism of neurokinin-1 receptor resensitization, we have studied the time courses of neurokinin-1 receptor responsiveness, recycling, and dephosphorylation by measuring cellular Ca(2+) responses, ligand-receptor binding, and receptor phosphorylation, respectively. Concentration-response curves and competition binding curves were obtained at various times following desensitization. The effects of the nonhydrolyzable GTP analog Gpp(NH)p on substance P binding were also studied to assess receptor-G protein coupling. After receptor activation and desensitization, Ca(2+) signaling in response to substance P occurred within 90 min, whereas the return of receptor binding required 240 min. Receptor dephosphorylation was greater than 90% complete 20 min after agonist washout. In addition, the return of substance P responsiveness coincided with a return in sensitivity of substance P binding to Gpp(NH)p, indicating a return in receptor-G protein coupling. These data show that the resensitization of responsiveness to substance P precedes receptor recycling. This may result from a conversion of nonfunctional neurokinin-1 receptors to functional receptors at the plasma membrane.
Identifier
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<a href="http://doi.org/10.1124/jpet.104.079954" target="_blank" rel="noreferrer noopener">10.1124/jpet.104.079954</a>
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2005
Adenosine Triphosphate/pharmacology
Animals
Bennett V J
Binding
Calcium/metabolism
CHO Cells
Competitive
Cricetinae
Guanylyl Imidodiphosphate/pharmacology
Neurokinin-1/*metabolism
Perrine S A
Phosphorylation
Rats
Receptors
Simmons M A
Substance P/metabolism
The Journal of pharmacology and experimental therapeutics