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Desensitization of the Neurokinin 1 Receptor Is Mediated by the Receptor Carboxy‐Terminal Region, but Is Not Caused by Receptor Internalization
Author(s) -
Sanders Matthew A.,
LeVine Harry
Publication year - 1996
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1996.67062362.x
Subject(s) - internalization , neurokinin a , receptor , tachykinin receptor 1 , homologous desensitization , biology , chinese hamster ovary cell , desensitization (medicine) , endocrinology , neurokinin b , chemistry , substance p , medicine , neuropeptide , biochemistry
The carboxy‐terminal cytoplasmic regions of the rat neurokinin 1 (substance P) and neurokinin 2 (neurokinin A) receptors have been exchanged to determine if this region of the neurokinin 1 receptor is involved in its desensitization. When expressed at similar levels in stably transfected Chinese hamster ovary (CHO) cell lines, receptors containing the carboxy‐terminal region of the neurokinin 1 receptor desensitized significantly more (as measured by reduction of the inositol 1,4,5‐trisphosphate response) when preexposed for 1 min to 1 µ M neurokinin, indicating a role for the carboxy‐terminal region of the neurokinin 1 receptor in its desensitization. Measurement of receptor internalization using radiolabeled neurokinins (0.3 n M ) indicated that ∼75–80% of the receptors were internalized in each cell line after 10 min at 37°C, with no observable correlation between neurokinin receptor desensitization and internalization. Measurement of loss of receptor surface sites for cell lines CHO NK1 and CHO NK1NK2 following exposure to 1 µ M substance P also indicated no obvious relationship between the percent desensitization and percent of receptors internalized. Also, two inhibitors of neurokinin 1 receptor internalization, phenylarsine oxide and hyperosmolar sucrose, did not inhibit neurokinin 1 receptor desensitization. The protein kinase inhibitors Ro 31‐8220, staurosporine, and Zn 2+ had no effect on neurokinin 1 receptor desensitization, indicating that the kinases affected by these agents are not rate‐limiting in neurokinin 1 receptor desensitization in this system.