The stimulatory effect of L-glutamate and related agents on inositol 1,4,5-trisphosphate production in the cestode Hymenolepis diminuta.
The effects of L-glutamate, acetylcholine, and serotonin (5HT) were examined on generation of inositol 1,4,5-triphosphate [Ins(1,4,5)P3], in membrane preparations of the cestode Hymenolepis diminuta. Only L-glutamate and acetylcholine stimulated a significant elevation in Ins(1,4,5)P3. The response to L-glutamate was stereospecific; D-glutamate or L-aspartate were not as potent. A role for G-protein(s) was supported by the observations that sodium fluoride stimulated Ins(1,4,5)P3 generation, and the L-glutamate response was potentiated by GTP and GTP-S and was suppressed by GDPS. However, studies with pertussis and cholera toxins indicated that the putative G-protein(s) was not pertussis or cholera toxin sensitive. The pharmacological profile of the L-glutamate response was examined partially. Trans-ACPD was a very effective agonist at 10(-5)M. While 10(-3)M L-glutamate, NMDA, and AMPA significantly elevated Ins(1,4,5)P3 levels, quisqualate and kainate did not. The elevation of Ins(1,4,5)P3 levels by L-glutamate and NMDA was antagonized by the specific glutamatergic antagonists AP-5, AP-7, CNQX, and CPP. While the response to ACPD was antagonized by AP5, CPP and CPG, CNQX was without effect. Collectively, the data support the hypothesis that in the cestode H. diminuta, L-glutamate activation of a metabotropic (ACPD) and/or ionotropic-like AMPA/NMDA receptor subtypes proceeds via a G protein(s) to enhance phospholipase C activity, ultimately resulting in the elevation of Ins(1,4,5)P3 levels in the tissues.
Samii
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Department of Biology, York University, Ontario, Canada.
Webb
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RA
D000109:Acetylcholine / Q000494:pharmacology; D000227:Adenine Nucleotides / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002772:Cholera Toxin / Q000494:pharmacology; D003470:Culture Media; D019204:GTP-Binding Proteins / Q000502:physiology; D018698:Glutamic Acid / Q000494:pharmacology*; D006150:Guanine Nucleotides / Q000494:pharmacology; D006926:Hymenolepis / Q000187:drug effects* / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis*; D012701:Serotonin / Q000494:pharmacology; D012969:Sodium Fluoride / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000227:Adenine Nucleotides; D003470:Culture Media; D006150:Guanine Nucleotides; D010566:Virulence Factors, Bordetella; D012701:Serotonin; D018698:Glutamic Acid; D015544:Inositol 1,4,5-Trisphosphate; D012969:Sodium Fluoride; D002772:Cholera Toxin; D019204:GTP-Binding Proteins; D000109:Acetylcholine; D002118:Calcium