Activation of muscarinic receptors stimulates GABA release in the rat globus pallidus

Abstract

The effect of carbachol on the spontaneous release of 3H-GABA was investigated on rat globus pallidus (GP) slices. Carbachol dose-dependently enhanced the release of 3H-GABA. The carbachol (5 x 10(-4) M) induced 3H-GABA release is mediated by muscarinic receptors since atropine (10(-6) M), pirenzepine (10(-6) M) and AF-DX384MS (10(-6) M) abolished the effect. An indirect carbachol effect mediated by dopaminergic and glutamatergic afferents was ruled out since the effect was not blocked by either D1 (SCH23390 10(-6) M) and D2 (sulpiride 10(-5) M) receptor antagonists or by ionotropic glutamate receptor antagonists (CNQX 10(-6) M and 10(-5) M, MK801 10(-6) M). A direct effect is further evidenced by the persistence of the carbachol effect in the presence of tetrodotoxin (5 x 10(-7) M). Surprisingly the carbachol effect was not abolished by lowering the Ca2+ concentration of the superfusion medium or by increasing concomitantly the Mg2+ concentration. The involvement of a GABA transporter can partially explain this latter result, as nipecotic acid (10(-3) M) blocked the effect by only 50%. Carbachol stimulated the accumulation of 3H-phosphoinositides in pallidal slices, an effect that was antagonized by atropine (10(-6) M), pirenzepine (10(-6) M), and AF-DX384MS (10(-6) M). These results suggest that the activation of muscarinic receptors localized on striatopallidal terminals stimulates the release of GABA in the globus pallidus through inositol phosphate hydrolysis.

Presynaptic nigral GPR55 receptors stimulate [3H]‐GABA release through [3H]‐cAMP production and PKA activation and promote motor behavior

“…GPR55 increases Ca 2+ release from intracellular stores in the dorsal root ganglion and hippocampal neurons (Lauckner et al, 2008;Sylantyev et al, 2013), modulating neuronal function. This dependence of presynaptic signaling from intracellular Ca 2+ stores also has been reported in the spontaneous and depolarization-induced GABA release from the cerebellum (Kelm et al, 2007), neocortex (Mathew & Hablitz, 2008), and globus pallidus (Jijon-Lorenzo et al, 2018;Kayadjanian et al, 1997).…”

Presynaptic nigral GPR55 receptors stimulate [3H]‐GABA release through [3H]‐cAMP production and PKA activation and promote motor behavior

“…GPR55 increases Ca 2+ release from intracellular stores in the dorsal root ganglion and hippocampal neurons (Lauckner et al, 2008;Sylantyev et al, 2013), modulating neuronal function. This dependence of presynaptic signaling from intracellular Ca 2+ stores also has been reported in the spontaneous and depolarization-induced GABA release from the cerebellum (Kelm et al, 2007), neocortex (Mathew & Hablitz, 2008), and globus pallidus (Jijon-Lorenzo et al, 2018;Kayadjanian et al, 1997).…”

Histamine H3Receptor Activation Counteracts Adenosine A2AReceptor-Mediated Enhancement of Depolarization-Evoked [3H]-GABA Release from Rat Globus Pallidus Synaptosomes

“…In this regard, in the rat GP, the release of GABA is inhibited by dopamine D 2 , serotonin 5-HT 1B , and group III metabotropic or kainate glutamate receptors, ,− and H 3 Rs inhibit the release of dopamine, serotonin, and glutamate. ,, However, H 3 R activation does not inhibit K + -evoked [ 3 H]-dopamine release from GP slices, and for glutamate and serotonin the predicted outcome of the activation of H 3 Rs located on the corresponding nerve terminals would be the disinhibition of GABA release, opposite to the results presented herein. Because the activation of muscarinic receptors stimulate spontaneous [ 3 H]-GABA release from rat GP slices and H 3 R activation reduces acetylcholine release, the H 3 R-mediated reduction in [ 3 H]-GABA release reported herein could also involve an indirect action due to the inhibition of depolarization-induced acetylcholine release from GP synaptosomes.…”

Cortical and nigral deafferentation and striatal cholinergic markers in the rat dorsal striatum: different effects on the expression of mRNAs encoding choline acetyltransferase and muscarinic m1 and m4 receptors

“…The differential changes in expression of the m1 and m4 mRNAs in the striatum after cortical and DA manipulations, respectively, may have functional consequences in the output structures of the striatum. Previous studies in our laboratory have shown a muscarinic modulation of GABA release in the globus pallidus (Kayadjanian et al, 1997) and the SN (Kayadjanian et al, 1994) via the activation of muscarinic receptors located on striatal afferents. Therefore, by affecting striatal m1 and m4 mRNA expression, the glutamatergic cortical and dopaminergic nigral systems could affect transmission of information in the two output structures of the striatum.…”

Presynaptic nigral GPR55 receptors stimulate [3H]‐GABA release through [3H]‐cAMP production and PKA activation and promote motor behavior

“…GPR55 increases Ca 2+ release from intracellular stores in the dorsal root ganglion and hippocampal neurons (Lauckner et al, 2008;Sylantyev et al, 2013), modulating neuronal function. This dependence of presynaptic signaling from intracellular Ca 2+ stores also has been reported in the spontaneous and depolarization-induced GABA release from the cerebellum (Kelm et al, 2007), neocortex (Mathew & Hablitz, 2008), and globus pallidus (Jijon-Lorenzo et al, 2018;Kayadjanian et al, 1997).…”

Histamine H3Receptor Activation Counteracts Adenosine A2AReceptor-Mediated Enhancement of Depolarization-Evoked [3H]-GABA Release from Rat Globus Pallidus Synaptosomes

“…In this regard, in the rat GP, the release of GABA is inhibited by dopamine D 2 , serotonin 5-HT 1B , and group III metabotropic or kainate glutamate receptors, ,− and H 3 Rs inhibit the release of dopamine, serotonin, and glutamate. ,, However, H 3 R activation does not inhibit K + -evoked [ 3 H]-dopamine release from GP slices, and for glutamate and serotonin the predicted outcome of the activation of H 3 Rs located on the corresponding nerve terminals would be the disinhibition of GABA release, opposite to the results presented herein. Because the activation of muscarinic receptors stimulate spontaneous [ 3 H]-GABA release from rat GP slices and H 3 R activation reduces acetylcholine release, the H 3 R-mediated reduction in [ 3 H]-GABA release reported herein could also involve an indirect action due to the inhibition of depolarization-induced acetylcholine release from GP synaptosomes.…”

Cortical and nigral deafferentation and striatal cholinergic markers in the rat dorsal striatum: different effects on the expression of mRNAs encoding choline acetyltransferase and muscarinic m1 and m4 receptors

“…The differential changes in expression of the m1 and m4 mRNAs in the striatum after cortical and DA manipulations, respectively, may have functional consequences in the output structures of the striatum. Previous studies in our laboratory have shown a muscarinic modulation of GABA release in the globus pallidus (Kayadjanian et al, 1997) and the SN (Kayadjanian et al, 1994) via the activation of muscarinic receptors located on striatal afferents. Therefore, by affecting striatal m1 and m4 mRNA expression, the glutamatergic cortical and dopaminergic nigral systems could affect transmission of information in the two output structures of the striatum.…”

Presynaptic nigral GPR55 receptors stimulate [3H]‐GABA release through [3H]‐cAMP production and PKA activation and promote motor behavior

“…GPR55 increases Ca 2+ release from intracellular stores in the dorsal root ganglion and hippocampal neurons (Lauckner et al, 2008;Sylantyev et al, 2013), modulating neuronal function. This dependence of presynaptic signaling from intracellular Ca 2+ stores also has been reported in the spontaneous and depolarization-induced GABA release from the cerebellum (Kelm et al, 2007), neocortex (Mathew & Hablitz, 2008), and globus pallidus (Jijon-Lorenzo et al, 2018;Kayadjanian et al, 1997).…”

Histamine H3Receptor Activation Counteracts Adenosine A2AReceptor-Mediated Enhancement of Depolarization-Evoked [3H]-GABA Release from Rat Globus Pallidus Synaptosomes

“…In this regard, in the rat GP, the release of GABA is inhibited by dopamine D 2 , serotonin 5-HT 1B , and group III metabotropic or kainate glutamate receptors, ,− and H 3 Rs inhibit the release of dopamine, serotonin, and glutamate. ,, However, H 3 R activation does not inhibit K + -evoked [ 3 H]-dopamine release from GP slices, and for glutamate and serotonin the predicted outcome of the activation of H 3 Rs located on the corresponding nerve terminals would be the disinhibition of GABA release, opposite to the results presented herein. Because the activation of muscarinic receptors stimulate spontaneous [ 3 H]-GABA release from rat GP slices and H 3 R activation reduces acetylcholine release, the H 3 R-mediated reduction in [ 3 H]-GABA release reported herein could also involve an indirect action due to the inhibition of depolarization-induced acetylcholine release from GP synaptosomes.…”

Cortical and nigral deafferentation and striatal cholinergic markers in the rat dorsal striatum: different effects on the expression of mRNAs encoding choline acetyltransferase and muscarinic m1 and m4 receptors

“…The differential changes in expression of the m1 and m4 mRNAs in the striatum after cortical and DA manipulations, respectively, may have functional consequences in the output structures of the striatum. Previous studies in our laboratory have shown a muscarinic modulation of GABA release in the globus pallidus (Kayadjanian et al, 1997) and the SN (Kayadjanian et al, 1994) via the activation of muscarinic receptors located on striatal afferents. Therefore, by affecting striatal m1 and m4 mRNA expression, the glutamatergic cortical and dopaminergic nigral systems could affect transmission of information in the two output structures of the striatum.…”