Similar Rates of Phosphatidylinositol Hydrolysis Following Activation of Wild-Type and Truncated Rat Neurokinin-1 Receptors
| Autor: | Crankshaw Cl, Raddatz R, James E. Krause, Snider Rm |
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| Rok vydání: | 2002 |
| Předmět: |
Time Factors
G protein Inositol Phosphates Substance P CHO Cells Biology Phosphatidylinositols Transfection Biochemistry Structure-Activity Relationship Cellular and Molecular Neuroscience chemistry.chemical_compound Cricetinae Homologous desensitization Tachykinin receptor 1 Animals Receptor G protein-coupled receptor Phospholipase C Biphenyl Compounds Receptors Neurokinin-1 Molecular biology Recombinant Proteins Rats chemistry Signal transduction Signal Transduction |
| Zdroj: | Journal of Neurochemistry. 64:1183-1191 |
| ISSN: | 0022-3042 |
| Popis: | The substance P (neurokinin-1) receptor belongs to the family of seven putative transmembrane domain receptors that are coupled via G proteins to phospholipase C activation. Homologous desensitization of substance P-stimulated responses has been described in various systems. The rat neurokinin-1 receptor and a truncated mutant lacking the carboxyl-terminal region were expressed in Chinese hamster ovary cells to examine the mechanisms of substance P-induced desensitization. Wild-type and truncated receptor-bearing cells were indistinguishable in agonist binding affinity and EC 50 of substance P-induced accumulation of 3 H-inositol phosphates. Substance P-induced responses continued for 30-45 min in cells expressing wild-type and truncated receptors as well as in rat LRM-55 and human U373 cells, which express endogenous neurokinin-1 receptors. In transfected cells expressing the wild-type receptor, CP-96,345 added 15 min after substance P blocked further responses, demonstrating the continuing presence of responsive receptors. The rates of accumulation of 3 H-inositol phosphates were four times greater in the initial 15 s of stimulation than for the next 20 min for both wildtype and truncated receptor types. This decrease in rate of substance P-stimulated phosphatidylinositol hydrolysis is therefore not dependent on the carboxyl-terminal region of the rat neurokinin-1 receptor, which contains 26 serine and threonine residues. These results are discussed in relation to current ideas regarding neurokinin-1 receptor desensitization |
| Databáze: | OpenAIRE |
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