5-Hydroxytryptamine-mediated increase in glutamate uptake by the leech giant glial cell.
The clearance of synaptically released glutamate is one of the pivotal functions of glial cells. We have studied the role of 5-hydroxytryptamine (5-HT, 30 microM), a neurotransmitter and neurohormone in the leech central nervous system with a versatile action spectrum, on the efficacy of glial glutamate uptake. The activity of the glutamate uptake carrier in the giant glial cell in isolated ganglia of Hirudo medicinalis was monitored by measuring the membrane current and the change in the intracellular Na(+) concentration (Na(+) (i)) as induced by the glutamate carrier substrate D-aspartate (D-asp, 1 mM). 5-HT increased the D-asp-induced current (EC(50) at 5 microM) and rise in Na(+) (i), an effect which was mimicked by the membrane-permeable cyclic nucleotide analogue dibutyryl-cyclic AMP (db-cAMP). The adenylyl cyclase inhibitor SQ 22,536 and the protein kinase A antagonist Rp-cAMP inhibited the effect of 5-HT. Blocking the G protein in the giant glial cell by injecting GDP-beta-S suppressed the effect of 5-HT, but not the effect of db-cAMP, on the D-asp-induced current. Our results suggest that 5-HT enhances the glial uptake of glutamate via cAMP- and PKA-mediated pathway.
Hirth
Ingolf C
IC
Abteilung für Allgemeine Zoologie, FB Biologie, Universität Kaiserslautern, Postfach 3049, D-67653 Kaiserslautern, Germany.
Deitmer
Joachim W
JW
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D027322:Amino Acid Transport System X-AG / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D003994:Bucladesine / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002490:Central Nervous System / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017952:Ganglia, Invertebrate / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D047709:Hirudo medicinalis / Q000166:cytology / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D018408:Patch-Clamp Techniques; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D012964:Sodium / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D000067956:Adenylyl Cyclase Inhibitors; D027322:Amino Acid Transport System X-AG; D004791:Enzyme Inhibitors; D043562:Receptors, G-Protein-Coupled; D001224:Aspartic Acid; D012701:Serotonin; D018698:Glutamic Acid; D003994:Bucladesine; D012964:Sodium; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases