GLUTAMATERGIC INOSITOL 1,4,5-TRISPHOSPHATE PRODUCTION IN TISSUE-SLICES OF THE CESTODE HYMENOLEPIS-DIMINUTA

The effects of L-glutamate and the glutamatergic agonists t-ACPD, AMPA , and NMDA on the Ins(1,4,5)P-3 levels in tissue slices of the cestode Hymenolepis diminuta were examined. The EC50's for the agonists showe d a rank order of potency of ACPD > NMDA > AMPA > L-glutamate. High co ncentrations of ligand produced inhibition which was likely caused by receptor desensitization. The effect of L-glutamate was abrogated by A P-5, CNQX, and CPG, while the effect of NMDA was diminished by AP-5, A P-7, CNQX, MK-801, and CPP. In contrast, the effect of t-ACPD was not significantly reduced by CPG. The pharmacology of the response to agon ists suggested that the receptors involved in elevation of Ins(1,4,5)P -3 levels were of the NMDA ionotropic type. Although elevation of Ins( 1,4,5)P-3 levels in membrane preparations of H. diminuta by L-glutamat e were effected predominantly through a G-protein, the elevation of In s(1,4,5)P-3 levels by L-glutamate in tissue slices was reduced to cont rol levels in the absence of external Ca2+. Fluoride, however, signifi cantly elevated Ins(1,4,5)P-3 levels in tissue slices, suggesting the occurrence of a G-protein linked receptor coupled to PLC in intact tis sues. The present evidence indicates that in H. diminuta, L-glutamate binds to ionotropic receptors which by a Ca2+ sensitive mechanism lead s to activation of PLC, some of which may be mediated by a G-protein. (C) 1997 Elsevier Science Inc.