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Possible cholinergic mechanism behind the galanin evoked acetylcholine release in the rat striatum
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Possible cholinergic mechanism behind the galanin evoked acetylcholine release in the rat striatum
Pramanik, A. and 0gren, S.O. Department of Histology and Neurobiology, Karolinska Institute, Box 60 400, S-I04 Ol Stockholm, Sweden Key words: Microdialysis; Galanin; Acetylcholine release; Striatum
Galanin (GAL), a 29-amino acid long, C-terminally amidated, biologically active neuropeptide(l), is widely distributed in the CNS and the PNS. Physiological roles of GAL have been intensively studied in the last years. Available evidences suggest that GAL is an inhibitory modulator of several neurotransmitters at both the pre- and postsynaptic levels. Recently we have for the first time demonstrated that GAL also possesses a facilitatory modulation of acetylcholine (ACh) in the rat striatum (2) most probably by a direct action of the peptide on striatal GAL receptors (3). The effect of GAL on the basal and the muscarinic agonist/antagonist mediated release of ACh was investigated in the anaesthetized rat using microdialysis and HPLC techniques. GAL (3 nmol/10 pl), applied in the lateral ventricle (i.c.v.) or perfused through the microdialysis membrane into the striatum, was found to enhance basal ACh release. GAL (3 nmol/10 /~l, i.c.v, or intrastriatally) was able to reverse the oxotremorine (0.3 mg/kg, i.p.) induced inhibition of ACh release but did not change the scopolamine (0.25 and 0.5 mg/kg, i.p.) or pirenzepine (1 pM, through the microdialysis membrane) stimulated release of ACh. The putative GAL antagonist M15 (3 nmol/10 pl, administered into the striatum) completely blocked the GAL evoked release of striatal ACh but did not inhibit the scopolamine (0.25 mg/kg, i.p.) stimulated ACh release, indicating that the mechanisms behind GAL and scopolamine evoked striatal ACh release differ. Our data indicate that stimulation of the basal ACh release by GAL in the strlatum occurs in strlatal intemeurons. This finding has significance for both the peptide functions and how peptide-receptor coregulatious may occur in the CNS. Further cholinergic mechanisms behind the GALstimulated ACh release in the rat striatum will be discussed. References
1. R6kaeus, A,. (1987), Galanin: a newly isolated biologically active neuropeptide. Trends Neurosci. 10, 158-164. 2. ()gren, S.O. and Pramanik, A. (1991), Galanin stimulates acetylcholine release in the rat slriatum. Neurosci. Lett. 128, 253-256. 3. Pramanik, A. and ()gren, S.O. (1992), Galanin evoked acetylcholine release in the rat strlatum is blocked by the putative galanin antagonist MI5. Brain Research 000, 000-000.
Possible cholinergic mechanism behind the galanin evoked acetylcholine release in the rat striatum
Pramanik, A. and 0gren, S.O. Department of Histology and Neurobiology, Karolinska Institute, Box 60 400, S-I04 Ol Stockholm, Sweden Key words: Microdialysis; Galanin; Acetylcholine release; Striatum
Galanin (GAL), a 29-amino acid long, C-terminally amidated, biologically active neuropeptide(l), is widely distributed in the CNS and the PNS. Physiological roles of GAL have been intensively studied in the last years. Available evidences suggest that GAL is an inhibitory modulator of several neurotransmitters at both the pre- and postsynaptic levels. Recently we have for the first time demonstrated that GAL also possesses a facilitatory modulation of acetylcholine (ACh) in the rat striatum (2) most probably by a direct action of the peptide on striatal GAL receptors (3). The effect of GAL on the basal and the muscarinic agonist/antagonist mediated release of ACh was investigated in the anaesthetized rat using microdialysis and HPLC techniques. GAL (3 nmol/10 pl), applied in the lateral ventricle (i.c.v.) or perfused through the microdialysis membrane into the striatum, was found to enhance basal ACh release. GAL (3 nmol/10 /~l, i.c.v, or intrastriatally) was able to reverse the oxotremorine (0.3 mg/kg, i.p.) induced inhibition of ACh release but did not change the scopolamine (0.25 and 0.5 mg/kg, i.p.) or pirenzepine (1 pM, through the microdialysis membrane) stimulated release of ACh. The putative GAL antagonist M15 (3 nmol/10 pl, administered into the striatum) completely blocked the GAL evoked release of striatal ACh but did not inhibit the scopolamine (0.25 mg/kg, i.p.) stimulated ACh release, indicating that the mechanisms behind GAL and scopolamine evoked striatal ACh release differ. Our data indicate that stimulation of the basal ACh release by GAL in the strlatum occurs in strlatal intemeurons. This finding has significance for both the peptide functions and how peptide-receptor coregulatious may occur in the CNS. Further cholinergic mechanisms behind the GALstimulated ACh release in the rat striatum will be discussed. References
1. R6kaeus, A,. (1987), Galanin: a newly isolated biologically active neuropeptide. Trends Neurosci. 10, 158-164. 2. ()gren, S.O. and Pramanik, A. (1991), Galanin stimulates acetylcholine release in the rat slriatum. Neurosci. Lett. 128, 253-256. 3. Pramanik, A. and ()gren, S.O. (1992), Galanin evoked acetylcholine release in the rat strlatum is blocked by the putative galanin antagonist MI5. Brain Research 000, 000-000.