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Presynaptic G Protein‐Coupled Receptors Differentially Modulate Spontaneous Glutamate Release in the Supraoptic Nucleus
Author(s) -
Muram S.,
Rowe T. M.,
Hirasawa M.
Publication year - 2016
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/jne.12329
Subject(s) - gabab receptor , metabotropic glutamate receptor , agonist , supraoptic nucleus , metabotropic receptor , forskolin , medicine , glutamate receptor , endocrinology , chemistry , inhibitory postsynaptic potential , biology , pharmacology , receptor , vasopressin , stimulation
Spontaneous glutamate release in the supraoptic nucleus is modulated by a number of inhibitory G protein coupled receptors ( GPCR ), including GABA B , adenosine A 1 and group III metabotropic glutamate receptors ( mG luR). It remains unclear whether they have distinct roles or are redundant mechanisms that protect from hyperexcitation. To address this question, we facilitated spontaneous glutamate release using nifedipine or forskolin, which act in a protein kinase A ( PKA) ‐independent and ‐dependent manner, respectively, and tested the effects of inhibitory GPCR agonists. We found that a GABAB receptor ( GABA B R ) agonist specifically inhibited forskolin‐induced miniature excitatory postsynaptic currents (mEPSC ), in contrast to an adenosine A1 receptor (A1R) agonist, which specifically inhibited nifedipine‐induced mEPSC s. This suggests that GABA B Rs and A 1 Rs modulate independent mechanisms activated by forskolin and nifedipine, respectively. However, the inhibitory effects of GABA B R and A 1 R agonists on basal mEPSC s occluded each other, suggesting that these receptors also have an overlapping role. Group III mG luRs appear to have a greater control over glutamate release because agonists to these receptors inhibited both nifedipine‐ and forskolin‐induced mEPSC s. mEPSC s induced by norepinephrine had the same characteristics as those induced by forskolin [i.e. PKA ‐dependence and sensitivity to GABA B R and group III mG luR agonists, but not an A 1 R agonist]. In summary, the present study highlights the differential effects of GABA B R , A 1 R and mG luR agonists on glutamate release stimulated by different secretagogues, including the endogenous neuromodulator norepinephrine. These results suggest that the roles of these inhibitory GPCR s are not completely redundant, and also indicate the physiological implications of having different excitatory and inhibitory GPCR s on the same synapse.