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External pH changes affect NMDA-evoked and spontaneous release of cholecystokinin, somatostatin and noradrenaline from rat cerebrocortical nerve endings
- Source :
-
Neurochemistry International . Oct2004, Vol. 45 Issue 5, p677-685. 9p. - Publication Year :
- 2004
-
Abstract
- It was previously reported that the K+-evoked release of somatostatin-like immunoreactivity (SRIF-LI) and of cholecystokinin-like immunoreactivity (CCK-LI) from superfused rat cerebrocortical synaptosomes can be enhanced by NMDA or d-serine alone. We here studied the effects of extraterminal pH changes on SRIF-LI and CCK-LI release. Lowering pH from 7.4 to 6.9 or 6.4 abolished the effects of NMDA or d-serine on the K+-evoked peptide release. Identical results were obtained when external pH was raised to 8 or 8.7. Sudden alkalinization of the superfusion medium, in absence of K+-depolarization, induced SRIF-LI or CCK-LI release which was insensitive to NMDA. Based on experiments in Ca2+-free medium and with voltage-sensitive Ca2+ channel (VSCC) blockers, the pH 8.7-induced release of SRIF-LI and CCK-LI was only in part (30–50%) dependent on external Ca2+ and Ca2+ channel activation. In contrast, the alkalinization-evoked release of [<F>3H</F>]noradrenaline was highly sensitive to external Ca2+ removal and to blockade of Ca2+ channels with ω-conotoxins. The pH 8.7-evoked SRIF-LI and CCK-LI was about halved in synaptosomes intoxicated with botulinum toxin C1. The results suggest that the pH-sensitive NMDA receptors mediating somatostatin and cholecystokinin release contain NR1 subunits lacking the exon-5 cassette. Alkalinization represents a novel releasing stimulus which elicits neuropeptide release in part by conventional exocytosis and largely by an external Ca2+-independent mechanism. Differently, the release of noradrenaline provoked by alkalinization occurs entirely by conventional exocytosis. [Copyright &y& Elsevier]
- Subjects :
- *SOMATOSTATIN
*GASTROINTESTINAL hormones
*CHOLECYSTOKININ
*NORADRENALINE
Subjects
Details
- Language :
- English
- ISSN :
- 01970186
- Volume :
- 45
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- Neurochemistry International
- Publication Type :
- Academic Journal
- Accession number :
- 13623284
- Full Text :
- https://doi.org/10.1016/j.neuint.2004.03.005