External pH changes affect NMDA-evoked and spontaneous release of cholecystokinin, somatostatin and noradrenaline from rat cerebrocortical nerve endings
| Autor: | Paolo Paudice, Fabio Longordo, Maurizio Raiteri, Anita Gemignani |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Male
medicine.medical_specialty Botulinum Toxins N-Methylaspartate Glycine Radioimmunoassay chemistry.chemical_element Neuropeptide Nitric Oxide Synthase Type I In Vitro Techniques Calcium Exocytosis Rats Sprague-Dawley Norepinephrine Cellular and Molecular Neuroscience Internal medicine Excitatory Amino Acid Agonists Serine medicine Animals Enzyme Inhibitors Cholecystokinin Cerebral Cortex Nerve Endings Voltage-dependent calcium channel Cell Biology Hydrogen-Ion Concentration Calcium Channel Blockers Rats Endocrinology Somatostatin chemistry Potassium Liberation NMDA receptor Calcium Channels Nitric Oxide Synthase Synaptosomes |
| Zdroj: | Neurochemistry International. 45:677-685 |
| ISSN: | 0197-0186 |
| DOI: | 10.1016/j.neuint.2004.03.005 |
| Popis: | 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 [3H]noradrenaline was highly sensitive to external Ca2+ removal and to blockade of Ca2+ channels with omega-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. |
| Databáze: | OpenAIRE |
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