Pharmacological Properties of the Type 1 Tyramine Receptor in the Diamondback Moth, Plutella xylostella.

Tyramine receptors (TARs) can be activated by tyramine (TA) or octopamine (OA) and have been shown to be related to physiological regulation (e.g., gustatory responsiveness, social organization, and learning behavior) in a range of insect species. A tyramine receptor gene in Plutella xylostella, Pxtar1, was cloned and stably expressed in the HEK-293 cell line. Pharmacological properties and expression profile of Pxtar1 were also analyzed. Tyramine could activate the PxTAR1 receptor, increasing the intracellular Ca2+ concentration ((Ca2+)i) at an EC50 of 13.1 nM and reducing forskolin (10 µM)-stimulated intracellular cAMP concentration ((cAMP)i) at an IC50 of 446 nM. DPMF (a metabolite of amitraz) and L(-)-carvone (an essential oil) were found to act as PxTAR1 receptor agonists. Conversely, yohimbine and mianserin had significant antagonistic effects on PxTAR1. In both larvae and adults, Pxtar1 had the highest expression in the head capsule and expression of Pxtar1 was higher in male than in female reproductive organs. This study reveals the temporal and spatial differences and pharmacological properties of Pxtar1 in P. xylostella and provides a strategy for screening insecticidal compounds that target PxTAR1.

The utility of excitatory amino acid (EAA) antagonists as analgesic agents. II. Assessment of the antinociceptive activity of combinations of competitive and non-competitive NMDA antagonists with agents acting at allosteric-glycine and polyamine receptor sites.

The present study examined the utility of using low-dose combinations of agents acting within the NMDA receptor complex to produce analgesic effects without producing motor dysfunction. In particular, we assessed the antinociceptive activity in the formalin test of combinations of competitive (APV) and non-competitive (MK-801) NMDA receptor antagonists with agonist and antagonists acting at allosteric-glycine and polyamine receptors. Both the competitive NMDA receptor antagonist APV and the non-competitive NMDA antagonist MK-801 produced dose-dependent analgesic effects in the late, but not the early, phase of the formalin test. The antinociceptive activity of APV was significantly enhanced by combination with a non-analgesic dose of the allosteric-glycine agonist glycine, and was reduced by combination with the allosteric-glycine antagonist 7-CKA which also reversed the glycine-induced enhancement of the antinociceptive effects of APV. The antinociceptive activity of MK-801 was significantly enhanced by combination with a non-analgesic dose of the polyamine agonist spermine, and reduced by combination with the polyamine receptor antagonist IFEN which also reversed the spermine-induced enhancement of the antinociceptive effects of MK-801. The enhancement of the antinociceptive activity of APV and MK-801 by glycine and spermine, respectively, was not accompanied by increases in motor dysfunction. Thus, by using specific combination of agents acting within the NMDA receptor complex, it was possible to produce effective antinociception in the formalin test at doses of NMDA receptor antagonists which did not produce motor dysfunction.