Activation of muscarinic receptors stimulates GABA release in the rat globus pallidus.
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.
Kayadjanian
N
N
Laboratoire de Neurochimie-Anatomie, CNRS URA 1488, Université Pierre et Marie Curie, Paris, France.
Menétrey
A
A
Besson
M J
MJ
D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005917:Globus Pallidus / Q000187:drug effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D011976:Receptors, Muscarinic; D005680:gamma-Aminobutyric Acid; D002217:Carbachol