Polyphosphoinositide metabolism in rat brain: effects of neuropeptides, neurotransmitters and cyclic nucleotides |
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Authors: | J Jolles C J van Dongen J ten Haaf W H Gispen |
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Affiliation: | 1. Division of Molecular Neurobiology, Rudolf Magnus Institute for Pharmacology Utrecht, The Netherlands;2. Laboratory of Physiological Chemistry, Medical Faculty, Utrecht, The Netherlands;3. Institute of Molecular Biology State University of Utrecht, Padualaan 8, 3508 TB Utrecht, The Netherlands |
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Abstract: | This study describes effects of various peptides, neurotransmitters and cyclic nucleotides on brain polyphosphoinositide metabolism in vitro. The interconversion of the polyanionic inositol phospholipids was studied by incubation of a lysed crude mitochondrial/synaptosomal fraction with [gamma-32P]-ATP. The reference peptide ACTH1-24 stimulated the formation of radiolabelled phosphatidylinositol 4,5-diphosphate (TPI) and inhibited that of phosphatidic acid (PA). Substance P inhibited both TPI and PA labelling, whereas beta-endorphin inhibited that of PA without any effect on TPI. Morphine had no effect at any concentration tested, whereas high concentrations of naloxone inhibited the labelling of both PA and TPI. Naloxone did not counteract the effects of ACTH1-24. The other peptides tested (lysine 8-vasopressin and angiotensin II) were without any effect. Under the conditions used, adrenaline, noradrenaline and acetylcholine did not affect the labelling of the (poly)phosphoinositides. Both dopamine and serotonin, however, dose-dependently inhibited the formation of radiolabelled TPI and PA. Low concentrations of cAMP stimulated TPI, but higher concentrations had an overall inhibitory effect on the labelling of TPI, PA and especially phosphatidylinositol 4-phosphate (DPI). The cyclic nucleotide did not mediate or counteract the effects of ACTH, and cGMP was without any effect. These results are discussed in the light of current ideas on the mechanism of action of neuropeptides. |
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Keywords: | ACTH β-Endorphin Polyphosphoinositides Phosphatidylinositol Substance P Opioids Cyclic nucleotides Neurotransmitters |
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