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

✍ Scribed by Nathalie Kayadjanian; Annie Menétrey; Marie-Jo Besson

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 111 KB
• Volume: 26
• Category: Article
• ISSN: 0887-4476
• DOI: 10.1002/(sici)1098-2396(199706)26:2<131::aid-syn4>3.0.co;2-9

✦ Synopsis

The effect of carbachol on the spontaneous release of 3 H-GABA was investigated on rat globus pallidus (GP) slices. Carbachol dose-dependently enhanced the release of 3 H-GABA. The carbachol (5 3 10 24 M) induced 3 H-GABA release is mediated by muscarinic receptors since atropine (10 26 M), pirenzepine (10 26 M) and AF-DX384MS (10 26 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 26 M) and D2 (sulpiride 10 25 M) receptor antagonists or by ionotropic glutamate receptor antagonists (CNQX 10 26 M and 10 25 M, MK801 10 26 M). A direct effect is further evidenced by the persistence of the carbachol effect in the presence of tetrodotoxin (5 3 10 27 M). Surprisingly the carbachol effect was not abolished by lowering the Ca 21 concentration of the superfusion medium or by increasing concomitantly the Mg 21 concentration. The involvement of a GABA transporter can partially explain this latter result, as nipecotic acid (10 23 M) blocked the effect by only 50%. Carbachol stimulated the accumulation of 3 H-phosphoinositides in pallidal slices, an effect that was antagonized by atropine (10 26 M), pirenzepine (10 26 M), and AF2DX384MS (10 26 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.