Tyramine receptor (SER-2) isoforms are involved in the regulation of pharyngeal pumping and foraging behavior in Caenorhabditis elegans
| Autor: | Elizabeth, Rex, Scott C, Molitor, Vera, Hapiak, Hong, Xiao, Megan, Henderson, Richard, Komuniecki |
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| Rok vydání: | 2004 |
| Předmět: |
Diagnostic Imaging
Models Molecular Serotonin Embryo Nonmammalian Time Factors Green Fluorescent Proteins DNA Recombinant Gene Expression Tyramine Nose Phosphatidylinositols Transfection Tritium Cell Line Animals Genetically Modified Radioligand Assay Receptors Biogenic Amine Chlorocebus aethiops Cyclic AMP Animals Humans Protein Isoforms Biogenic Monoamines Drug Interactions Amino Acid Sequence RNA Messenger Cloning Molecular Caenorhabditis elegans Octopamine Adrenergic Uptake Inhibitors Behavior Animal Dose-Response Relationship Drug Reverse Transcriptase Polymerase Chain Reaction Cell Membrane Feeding Behavior Embryo Mammalian Lysergic Acid Diethylamide Phenotype Pertussis Toxin Pharynx Calcium Extracellular Space Adrenergic alpha-Agonists |
| Zdroj: | Journal of neurochemistry. 91(5) |
| ISSN: | 0022-3042 |
| Popis: | Octopamine regulates essential processes in nematodes; however, little is known about the physiological role of its precursor, tyramine. In the present study, we have characterized alternatively spliced Caenorhabditis elegans tyramine receptor isoforms (SER-2 and SER-2A) that differ by 23 amino acids within the mid-region of the third intracellular loop. Membranes prepared from cells expressing either SER-2 or SER-2A bind [3H]lysergic acid diethylamide (LSD) in the low nanomolar range and exhibit highest affinity for tyramine. Similarly, both isoforms exhibit nearly identical Ki values for a number of antagonists. In contrast, SER-2A exhibits a significantly lower affinity than SER-2 for other physiologically relevant biogenic amines, including octopamine. Pertussis toxin treatment reduces affinity for both tyramine and octopamine, especially for octopamine in membranes from cells expressing SER-2, suggesting that the conformation of the mid-region of the third intracellular loop is dictated by G-protein interactions and is responsible for the differential tyramine/octopamine affinities of the two isoforms. Tyramine reduces forskolin-stimulated cAMP levels in HEK293 cells expressing either isoform with nearly identical IC50 values. Tyramine, but not octopamine, also elevates Ca2+ levels in cells expressing SER-2 and to a lesser extent SER-2A. Most importantly, ser-2 null mutants (pk1357) fail to suppress head movements while reversing in response to nose-touch, suggesting a role for SER-2 in the regulation of foraging behavior, and fail to respond to tyramine in assays measuring serotonin-dependent pharyngeal pumping. These are the first reported functions for SER-2. These results suggest that C. elegans contains tyramine receptors, that individual SER-2 isoforms may differ significantly in their sensitivity to other physiologically relevant biogenic amines, such as octopamine (OA), and that tyraminergic signaling may be important in the regulation of key processes in nematodes. |
| Databáze: | OpenAIRE |
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