• Molecules and Cells
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• v.46 no.7
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• pp.451-460
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• 2023

Animals generally prefer nutrients and avoid toxic and harmful chemicals. Recent behavioral and physiological studies have identified that sweet-sensing gustatory receptor neurons (GRNs) in Drosophila melanogaster mediate appetitive behaviors toward fatty acids. Sweet-sensing GRN activation requires the function of the ionotropic receptors IR25a, IR56d, and IR76b, as well as the gustatory receptor GR64e. However, we reveal that hexanoic acid (HA) is toxic rather than nutritious to D. melanogaster. HA is one of the major components of the fruit Morinda citrifolia (noni). Thus, we analyzed the gustatory responses to one of major noni fatty acids, HA, via electrophysiology and proboscis extension response (PER) assay. Electrophysiological tests show this is reminiscent of arginine-mediated neuronal responses. Here, we determined that a low concentration of HA induced attraction, which was mediated by sweet-sensing GRNs, and a high concentration of HA induced aversion, which was mediated by bitter-sensing GRNs. We also demonstrated that a low concentration of HA elicits attraction mainly mediated by GR64d and IR56d expressed by sweet-sensing GRNs, but a high concentration of HA activates three gustatory receptors (GR32a, GR33a, and GR66a) expressed by bitter-sensing GRNs. The mechanism of sensing HA is biphasic in a dose dependent manner. Furthermore, HA inhibit sugar-mediated activation like other bitter compounds. Taken together, we discovered a binary HA-sensing mechanism that may be evolutionarily meaningful in the foraging niche of insects.

• The Korean Journal of Pain
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• v.13 no.2
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• pp.137-142
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• 2000

Background: Systemic or intrathecal administration of gabapentin has been shown to reverse various pain states. However, until now, the effect of intracerebroventricular (ICV) gabapentin to noxious stimuli has not been reported. The authors' aim of this study was to determine the effect of ICV gabapentin on the inflammatory nociceptive model, formalin test, in rats. Methods: ICV catheters were implanted under halothane anesthesia. For the nociceptive test, $50{\mu}l$ of 5% formalin was subcutaneously injected into the hindpaw. The effect of ICV gabapentin, administered 10 min before formalin injection, were examined on flinching, mean arterial pressure and heart rate evoked by a injection of formalin. Results: Injection of formalin into the paw resulted in a biphasic flinching and cardiovascular response. ICV gabapentin produced a dose-dependent suppression of the flinching and mean arterial pressure response during phase 1. In contrast, in phase 2, ICV gabapentin did not attenuate the pain behavior. ICV gabapentin did not affect on the baseline mean arterial pressure and heart rate. Conclusions: ICV gbapentin was effective for the acute noxious stimulus but it had no effect on the facilitated states induced by tissue injury.

• The Korean Journal of Pharmacology
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• v.25 no.1
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• pp.23-30
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• 1989

Buprenorphine, one of the mixed agonist-antagonist opioid drugs was used to inverstigate the opioid receptor on frog sciatic nerve A fibers. Action potentials were recorded for 4 hrs by a sucrose gap apparatus which were separated by four rubber membranes. To examine the one of the mechanism of action of buprenorphine, meperidine or naloxone was added after or before the treatment of buprenorphine. The results of this experiment were as follows: 1. Buprenorphine suppressed significantly the compound action potentials of frog sciatic nerve, and the maximal effects were shown both at $10^{-4}\;M$ and at $10^{-8}\;M$. 2. The dose-response relationship of buprenorphine on the depressant effect in frog sciatic nerve was biphasic and inverted U-shaped. 3. Buprenorphine blocked the effect of Meperidine $(10^{-3}\;M)$ on this preparation. 4. The depressant effcct of Buprenorphine on frog sciatic nerve was blocked by $10^{-8}\;M$ naloxone. From the above results, buprenorphine acts as one of agoinist-antagonistic effect on frog sciatic nerve, and the opioid receptor on this preparation is located on or near the intracellular opening of the sodium channels, which are sensitive to naloxone.

• Journal of Periodontal and Implant Science
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• v.27 no.4
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• pp.805-818
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• 1997

Immune responses of periodontal tissue may be regulated by products of sensory afferent nerve endings such as neuropeptides. Substance P(SP), a tachykinin neuropeptide, has been previously reported to stimulate the activities of T lymphocyte. Therefore, I examined the role of SP in IL-2 production and cell proliferation by using a homogeneous line of T lymphocytes(Jurkat and HuT78). Cell proliferation rate was determined by [$^3H$]-thymidine incorporation test, and IL-2 was quantitated by the growth rate of CD4+ IL-2-dependent T lymphocyte line CTLL-2. SP stimulated cell proliferation of T lymphocytes at the concentration of $10^{-12}$ and $10^{-8}$M in a biphasic bell-shape dose-dependent manner. However, SP alone did not induce IL-2 release at the concentration range of $10^{-6}$ to $10^{-14}$M. The upregulation of IL-2 release was observed when $10^{-12}$M SP was applied together with mitogens such as Con A or PHA+PMA on T cell lines, especially on Jurkat. Con A or PHA+PMA demonstrated to increase the rate of cell proliferation of Jurkat, which had shown to produce much amount of IL-2 indicating that mitogen-induced cell proliferation might be partially influenced by released IL-2. It was concluded that regulatory effects of SP on the immune/inflammatory response could be mediated through the costimulatory upregulation of IL-2 production and increase of cell proliferation of T lymphocyte.

• The Korean Journal of Pharmacology
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• v.26 no.1
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• pp.13-23
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• 1990

Methylene Blue (MeB) and gentian violet $(10^{-6}{\sim}10^{-4}\;M)$ produced contractions in isolated thoracic aortic preparations of rabbits in a dose-dependent fashion, while other dyes, evans blue and eosine yellowish, did not affect the basal tension in the same range of doses. Porcine mesenteric arterial rings also responded to MeB with dose-dependent contractions. Single dose of $10^{-4}$ M MeB produced a biphasic response: contraction followed by relaxation. The contraction developed slowly within $2{\sim}4$ min and peaked in about 20 minutes and then slowly relaxed to the basal level. Tyramine $(10^{-4}\;M)$ also induced contraction but it developed faster and was more persistent than that of MeB. While the tyramine-induced tension was reproducible, the MeB-induced one wat not reiterable until 3 to 5 hours after washing out the MeB. Adding $10^{-4}$ M MeB further potentiated the contraction induced by $10^{-4}$ M tyramine. However, the MeB contraction was not affected by further addition or tyramine. Both tyramine- and MeB-induced tensions were abolished or significantly inhibited by pretreatment with various drugs acting on the sympathetic nervous system. The tyramine-induced tension was more sensitive to guanethidine and 6-hydroxydopamine than the MeB-induced tension, while the latter was more sensitive to $Ca^{2+}-free$ PSS and reserpine. But they have similar sensitivity to prazosin. The MeB-induced tension was significantly inhibited but not abolished by 6-hydroxydopamine pretreatment. However, either tyramine or 6-hydroxydopamine could not affect the basal tension of the ring that MeB once had been tested. These results suggest that MeB-induced contractions of rabbit thoracic aorta and porcine mesenteric artery result from a release of endogenous norepinephrine from adrenergic nerve endings and are dependent in part on extracellular calcium, and that the potency of MeB to release or to deplete norepinephrine is greater than that of either tyramine or 6-hydroxydopamine.