Is the muscarinic receptor that mediates potentiation of dopamine release negatively coupled to the cyclic GMP system?

Dopamine (DA) terminals in rat corpus striatum and frontal cortex possess muscarinic receptors that mediate enhancement of the depolarization-evoked release of the catecholamine. The effects of the membrane-permeating cyclic guanosine monophosphate (cyclic GMP) analog 8-Br-cyclic GMP and of the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX) on the muscarinic-induced increase of DA release were investigated in striatal synaptosomes prelabeled with [3H]DA and exposed in superfusion to 15 mM KCl and to acetylcholine (ACh). Preincubation of synaptosomes with 8-Br-cyclic GMP (10-200 microM) or with IBMX (200 microM) prevented the ACh-induced enhancement of [3H]DA release, without affecting the K+-evoked release of the [3H]amine. No significant decrease of the ACh effect was observed when 8-Br-cyclic GMP or IBMX were added concomitantly with ACh to the superfusion medium. The data suggest that stimulation of presynaptic muscarinic receptors on DA terminals may produce enhancement of 3H DA release through a decrease of the intraterminal cyclic GMP content.