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Galanin affects REM sleep and nonREM sleep without changing nocturnal hormonal secretion in man
Abstracts from the l l th htternational Symposium on Regulatory Peptides
Determination of sorting related structures in human progastrin Christina Munksgaard, Jens F. Rehfeld and Jens R. Bundgaard Dept. of Clin. Biochem., National University Hospital, Copenhagen, Denmark. Upon biosynthesis, secretory proteins are transported to the Golgi complex where they are sorted to either of the two different secretory pathways- the constitutive and the regulated pathway. Propeptides are sorted to the regulated pathway resulting in maturation to the bioactive form and storage in secretory granules that are released in response to extracellular stimuli. The molecular basis of peptide sorting to the regulated secretory pathway is poorly understood, but it is believed that sorting to the regulated pathway is an active process whereas constitutive secretion is the default pathway. Current models of active sorting to the regulated pathway include the specific selection of target proteins by a putative sorting receptor-like structure, or that aggregation of secretory proteins in itself is sufficient to direct regulated secretion. It has also been proposed that helper proteins, such as the grenins, act in sorting by participation in aggregation of other proteins and that they themselves carry a putative sorting signal recognised by a 'sorting receptor'. Gastrin is a hormone that stimulates gastric acid secretion and growth of the gastrointestinal mucosa. It is released from antral G-cells into the blood stream in response to various stimuli. We have established a gene transfer system in an endocrine cell line to examine the biosynthesis of human gastrin, and we are now using the system to analyse structural determinants in progastrin involved in sorting to the regulated pathway. This is accomplished by deletion analysis combined with transfer of progastrin fragments to a constitutively secreted reporter protein. The study should reveal structurally important features in progastrin trafficking, regardless of the sorting mechanism.
Galanin affects REM sleep and nonREM sleep without changing nocturnal hormonal secretion in man H. Murck, P. Maier, R.M. Frieboes, T. Schier, F. Holsboer, A.Steiger Max Planck Institute of Psychiatry, Clinical Institute, Department of Psychiatry, Kraepelinstrasse 10, D-80804 Munich, Germany Galanin decreases the activity of locus coeruleus (LC) neurons of rats in vitro (Seutin et al., Eur. J. Pharmacol, 164, 1988). This structure is known to be involved in the REM-nREM sleep regulation (Hobson et al., J. Neurophysiol. 37, 1994). Furthermore REM sleep deprivation leads to an induction of galanin gene expression in rats (Toppila et al., Neurosci. Lett. 183, 1995). We studied the effects of 4 x 50/~g galanin (n = 9) and of 4 x 150 ktg galanin (n = 8) hourly administered as intravenous boluses between 22 h and 1 h on sleep EEG and nocturnal hormonal secretion in normal male controls. 4 x 50/~g galanin resulted in a trend to an increase in REM sleep for the first 3 sleep cycles (16.8 + 9.8 rain after placebo vs. 22.9 + 12.1 rain after galanin, p<0.07) and a reduction of stage 2 sleep for sleep period time (253.1 + 20.1 rain vs. 228.5 + 28.2 min, p<0.01). After 4 x 150 ~g galanin REM sleep increased tendentially for the first 3 sleep cycles with a significant increase in REM sleep duration during the third cycle (19.9 + 11.8 min vs. 35.1 + 13.9 rain, p<0.02). Spectral analysis revealed a significant increase in delta power frequency range for the sleep period time after the lower (268.1 + 51,3/LV 2 vs. 324.5 + 74.1 ~tV2, p<0.05), but not after the higher dosage of galanin. The secretion of growth hormone, cortisol and prolactin remained unchanged in either protocol. Our data are consistent with the assumption of a direct effect of galanin on the LC. (Supported by the DFG, Ste 486/1-2).
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Determination of sorting related structures in human progastrin Christina Munksgaard, Jens F. Rehfeld and Jens R. Bundgaard Dept. of Clin. Biochem., National University Hospital, Copenhagen, Denmark. Upon biosynthesis, secretory proteins are transported to the Golgi complex where they are sorted to either of the two different secretory pathways- the constitutive and the regulated pathway. Propeptides are sorted to the regulated pathway resulting in maturation to the bioactive form and storage in secretory granules that are released in response to extracellular stimuli. The molecular basis of peptide sorting to the regulated secretory pathway is poorly understood, but it is believed that sorting to the regulated pathway is an active process whereas constitutive secretion is the default pathway. Current models of active sorting to the regulated pathway include the specific selection of target proteins by a putative sorting receptor-like structure, or that aggregation of secretory proteins in itself is sufficient to direct regulated secretion. It has also been proposed that helper proteins, such as the grenins, act in sorting by participation in aggregation of other proteins and that they themselves carry a putative sorting signal recognised by a 'sorting receptor'. Gastrin is a hormone that stimulates gastric acid secretion and growth of the gastrointestinal mucosa. It is released from antral G-cells into the blood stream in response to various stimuli. We have established a gene transfer system in an endocrine cell line to examine the biosynthesis of human gastrin, and we are now using the system to analyse structural determinants in progastrin involved in sorting to the regulated pathway. This is accomplished by deletion analysis combined with transfer of progastrin fragments to a constitutively secreted reporter protein. The study should reveal structurally important features in progastrin trafficking, regardless of the sorting mechanism.
Galanin affects REM sleep and nonREM sleep without changing nocturnal hormonal secretion in man H. Murck, P. Maier, R.M. Frieboes, T. Schier, F. Holsboer, A.Steiger Max Planck Institute of Psychiatry, Clinical Institute, Department of Psychiatry, Kraepelinstrasse 10, D-80804 Munich, Germany Galanin decreases the activity of locus coeruleus (LC) neurons of rats in vitro (Seutin et al., Eur. J. Pharmacol, 164, 1988). This structure is known to be involved in the REM-nREM sleep regulation (Hobson et al., J. Neurophysiol. 37, 1994). Furthermore REM sleep deprivation leads to an induction of galanin gene expression in rats (Toppila et al., Neurosci. Lett. 183, 1995). We studied the effects of 4 x 50/~g galanin (n = 9) and of 4 x 150 ktg galanin (n = 8) hourly administered as intravenous boluses between 22 h and 1 h on sleep EEG and nocturnal hormonal secretion in normal male controls. 4 x 50/~g galanin resulted in a trend to an increase in REM sleep for the first 3 sleep cycles (16.8 + 9.8 rain after placebo vs. 22.9 + 12.1 rain after galanin, p<0.07) and a reduction of stage 2 sleep for sleep period time (253.1 + 20.1 rain vs. 228.5 + 28.2 min, p<0.01). After 4 x 150 ~g galanin REM sleep increased tendentially for the first 3 sleep cycles with a significant increase in REM sleep duration during the third cycle (19.9 + 11.8 min vs. 35.1 + 13.9 rain, p<0.02). Spectral analysis revealed a significant increase in delta power frequency range for the sleep period time after the lower (268.1 + 51,3/LV 2 vs. 324.5 + 74.1 ~tV2, p<0.05), but not after the higher dosage of galanin. The secretion of growth hormone, cortisol and prolactin remained unchanged in either protocol. Our data are consistent with the assumption of a direct effect of galanin on the LC. (Supported by the DFG, Ste 486/1-2).
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