Metabotropic and NMDA glutamate receptor interactions with osmotic stimuli in supraoptic neurons.
During increases in plasma osmolality, the actions of extrinsic glutamatergic synaptic inputs on magnocellular neuroendocrine cells (MNCs) are thought to combine with intrinsic osmosensitivity of these cells to promote the release of vasopressin (VP). In the present study, changes in intracellular calcium were used as an endpoint to examine putative interactions between osmotic stimuli and NMDA and metabotropic glutamate receptors (mGluRs). Exposure of MNCs to hyperosmotic solutions resulted in a very small, gradual increase in intracellular calcium. NMDA (100-300 microM) combined with osmotic stimulation gave rise to a synergistic increase in intracellular calcium. The broad spectrum mGluR agonist, (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) and the type I mGluR agonist, (RS)-3,5-dihydroxyphenylglycine (DHPG) evoked an acute calcium rise followed by a sustained increase. However, when combined with the hyperosmotic stimulus, the calcium responses to 1S,3R-ACPD and DHPG were suppressed. The type II agonist, (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV), and the type III agonist, (+)-2-amino-4-phosphonobutyric acid (AP-4), facilitated the loss of calcium from the MNCs and were largely unaffected by the osmotic stimulus. These osmotic interactions with NMDA and mGluR function not only help to explain the mechanisms that underlie osmotically mediated changes in MNC function, but also have implications for the impact of hyperosmotic stress in various pathological conditions.
Department of Neurology, CB# 7025, 781 Burnett-Womack Bldg., University of North Carolina, Chapel Hill, NC 27599, USA. meekerr@glial.med.unc.edu
Rick B
RB
Meeker
D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003521:Cyclopropanes / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007091:Image Processing, Computer-Assisted; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives* / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D009490:Neurosecretory Systems / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009994:Osmolar Concentration; D011247:Pregnancy; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D013495:Supraoptic Nucleus / Q000166:cytology* / Q000187:drug effects*
D003521:Cyclopropanes; D018690:Excitatory Amino Acid Agonists; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; C082313:2-(2,3-dicarboxycyclopropyl)glycine; D008734:Methoxyhydroxyphenylglycol; D016202:N-Methylaspartate; D005998:Glycine; C010117:3,4-dihydroxyphenylglycol