Galanin stimulates striatal acetylcholine release via a mechanism unrelated to cholinergic receptor stimulation.Regul Pept. 1993 Jun 11; 45(3):353-62.RP
The effect of galanin (GAL) on the basal and the muscarinic agonist/antagonist mediated release of acetylcholine (ACh) in the striatum was investigated in male rats using in vivo microdialysis and HPLC techniques. GAL (300 microM or 3 nmol/10 microliters), perfused through the microdialysis membrane into the striatum, was found to enhance basal ACh release. The GAL evoked ACh release was completely prevented by bupivacaine, a sodium channel blocker (1.5 mM) when coperfused with GAL. This suggests that the effect of GAL depends on intact neuronal activity and thus derives from impulse-dependent release. The muscarinic agonists oxotremorine (0.3 mg/kg, i.p.) or carbachol (100 microM, infusion) reduced ACh release and reduced the stimulation of ACh release by GAL with a magnitude corresponding to that of oxotremorine or carbachol alone. Thus, the resultant effect of GAL on ACh release remained unchanged. When GAL was given at a threshold dose (30 microM), which by itself did not stimulate ACh release, it was unable to attenuate the muscarinic agonist induced inhibition of ACh releases. Furthermore, GAL given in combination with scopolamine (0.25 mg/kg, i.p.) or pirenzepine (1 microM, infusion) added to the stimulating effect by the two muscarinic antagonists. In contrast to the GAL (300 microM) evoked ACh release, the scopolamine (0.25 mg/kg, i.p.) stimulated ACh release was not blocked by M15, a putative GAL antagonist, indicating that the mechanisms behind GAL and scopolamine evoked striatal ACh release differ. These results suggest that the mechanisms behind GAL evoked release do not involve direct interactions with pre- or postsynaptic muscarinic receptor mediated events. It is concluded that the stimulation of the basal ACh release by GAL in the striatum occurs via occupation of GAL receptors located on cholinergic interneurons and that the release process is dependent on intact neuronal activity.