Article

Tyramine receptor (SER-2) isoforms are involved in the regulation of pharyngeal pumping and foraging behavior in Caenorhabditis elegans.

Department of Biological Sciences, University of Toledo, Toledo, Ohio3606-3390, USA.
Journal of Neurochemistry (Impact Factor: 3.97). 01/2005; 91(5):1104-15. DOI: 10.1111/j.1471-4159.2004.02787.x
Source: PubMed

ABSTRACT 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.

0 Bookmarks
 · 
63 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Ascaris lumbricoides is the most prevalent soil-transmitted helminth (STH) infection of human beings worldwide. Chemotherapy with synthetic anthelmintics such as albendazole, mebendazole, and pyrantel pamoate is the current method of treatment; however, the emergence of anthelmintic resistance could substantially decrease the efficacy of such treatments and the sustainability of STH control programs. Additionally, benzimidazoles are not recommended for pregnant women or children under age one. A blinded, controlled study was conducted to evaluate the efficacy of two microencapsulated, plant-based essential oil blends, TTN1013 (α-pinene, linalyl acetate, p-cymene, and thymol octanoate) and TTN1014 (α-pinene, linalyl acetate, p-cymene, and thymol acetate) as functional foods against Ascaris suum infection in pigs, an important pathogen that closely resembles human infections with A. lumbricoides. Four groups of 16 female, 21-24 day old, Yorkshire-cross pigs were treated daily with 0.5 or 1.0mg/kg TTN1013, 1.0mg/kg TTN1014, or 1.0mg/kg equivalent of empty capsules, delivered inside a cream-filled sandwich cookie for 14 weeks. Three days after the initiation of daily treatments, pigs were inoculated daily with A. suum eggs for 4 weeks. Pigs were weighed weekly and fecal egg counts (FEC) were conducted weekly starting five weeks after initial inoculation with A. suum eggs. Fourteen weeks after first infection with eggs, pigs were necropsied and worms were recovered, counted and separated according to sex. TTN1013 administered daily at a dose of 1.0mg/kg yielded a statistically significant reduction in total worm counts (76.8%), female worm counts (75.5%), FEC (68.6%), and worm volume (62.9%) when compared to control group. Reduction of total and female worm numbers and FEC were not significant for TTN1014 or at the 0.5mg/kg dose of TTN1013. All treatments were well-tolerated by all pigs and did not cause any adverse reactions. All pigs remained clinically normal and showed no signs of reduced intestinal health for the duration of treatment. Based on these results, TTN1013 shows promise as a daily supplement to reduce infection burdens of soil transmitted helminths in both pigs and human beings.
    Acta tropica. 06/2014;
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The olfactory response of the vinegar fly Drosophila melanogaster to food odor is modulated by starvation. Here we show that this modulation is not restricted to food odors and their detecting sensory neurons but rather increases the behavioral response to odors as different as food odors, repellents and pheromones. The increased behavioral responsiveness is paralleled by an increased physiological sensitivity of sensory neurons regardless whether they express olfactory or ionotropic receptors and regardless whether they are housed in basiconic, coeloconic, or trichoid sensilla. Silencing several genes that become up-regulated under starvation confirmed the involvement of the short neuropeptide f receptor in the starvation effect. In addition it revealed that the CCHamide-1 receptor is another important factor governing starvation-induced olfactory modifications.
    Scientific Reports 09/2013; 3:2765. · 5.08 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Monoamines and neuropeptides interact to modulate most behaviors. To better understand these interactions, we have defined the roles of tyramine (TA), octopamine, and neuropeptides in the inhibition of aversive behavior in Caenorhabditis elegans. TA abolishes the serotonergic sensitization of aversive behavior mediated by the two nociceptive ASH sensory neurons and requires the expression of the adrenergic-like, Gαq-coupled, TA receptor TYRA-3 on inhibitory monoaminergic and peptidergic neurons. For example, TA inhibition requires Gαq and Gαs signaling in the peptidergic ASI sensory neurons, with an array of ASI neuropeptides activating neuropeptide receptors on additional neurons involved in locomotory decision-making. The ASI neuropeptides required for tyraminergic inhibition are distinct from those required for octopaminergic inhibition, suggesting that individual monoamines stimulate the release of different subsets of ASI neuropeptides. Together, these results demonstrate that a complex humoral mix of monoamines is focused by more local, synaptic, neuropeptide release to modulate nociception and highlight the similarities between the tyraminergic/octopaminergic inhibition of nociception in C. elegans and the noradrenergic inhibition of nociception in mammals that also involves inhibitory peptidergic signaling.
    Journal of Neuroscience 08/2013; 33(35):14107-16. · 6.91 Impact Factor

Full-text

Download
0 Downloads