Two neuropeptides recruit different messenger pathways to evoke Ca2+ signals in the same cell.
Bombesin and cholecystokinin (CCK) peptides act as signalling molecules in both the central nervous system and gastrointestinal tract [1-4]. It was reported recently that nicotinic acid adenine dinucleotide phosphate (NAADP) releases Ca2+ from mammalian brain microsomes [5] and triggers Ca2+ signals...
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Formaat: | Journal article |
Taal: | English |
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2000
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author | Burdakov, D Galione, A |
author_facet | Burdakov, D Galione, A |
author_sort | Burdakov, D |
collection | OXFORD |
description | Bombesin and cholecystokinin (CCK) peptides act as signalling molecules in both the central nervous system and gastrointestinal tract [1-4]. It was reported recently that nicotinic acid adenine dinucleotide phosphate (NAADP) releases Ca2+ from mammalian brain microsomes [5] and triggers Ca2+ signals in pancreatic acinar cells, where it is proposed to mediate CCK-evoked Ca2+ signals [6]. Here, for the first time, we have finely resolved bombesin-induced cytosolic Ca2+ oscillations in single pancreatic acinar cells by whole-cell patch-clamp monitoring of Ca2+-dependent ionic currents [6-8]. Picomolar concentrations of bombesin and CCK evoked similar patterns of cytosolic Ca2+ oscillations, but high, desensitising, NAADP concentrations selectively inhibited CCK, but not bombesin-evoked signals. Inhibiting inositol trisphosphate (IP3) receptors with a high concentration of caffeine blocked both types of oscillations. We further tested whether NAADP is involved in Ca2+ signals triggered by activation of the low-affinity CCK receptor sites. Nanomolar concentrations of CCK evoked non-oscillatory Ca2+ signals, which were not affected by desensitising NAADP receptors. Our results suggest that Ca2+-release channels gated by the novel Ca2+-mobilising molecule NAADP are only essential in specific Ca2+-mobilising pathways, whereas the IP3 receptors are generally required for Ca2+ signals. Thus, the same cell may use different combinations of intracellular Ca2+-releasing messengers to encode different external messages. |
first_indexed | 2024-03-07T06:58:36Z |
format | Journal article |
id | oxford-uuid:fefbd4ef-e794-4c1c-80b9-87b8cee7d588 |
institution | University of Oxford |
language | English |
last_indexed | 2024-03-07T06:58:36Z |
publishDate | 2000 |
record_format | dspace |
spelling | oxford-uuid:fefbd4ef-e794-4c1c-80b9-87b8cee7d5882022-03-27T13:40:58ZTwo neuropeptides recruit different messenger pathways to evoke Ca2+ signals in the same cell.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:fefbd4ef-e794-4c1c-80b9-87b8cee7d588EnglishSymplectic Elements at Oxford2000Burdakov, DGalione, ABombesin and cholecystokinin (CCK) peptides act as signalling molecules in both the central nervous system and gastrointestinal tract [1-4]. It was reported recently that nicotinic acid adenine dinucleotide phosphate (NAADP) releases Ca2+ from mammalian brain microsomes [5] and triggers Ca2+ signals in pancreatic acinar cells, where it is proposed to mediate CCK-evoked Ca2+ signals [6]. Here, for the first time, we have finely resolved bombesin-induced cytosolic Ca2+ oscillations in single pancreatic acinar cells by whole-cell patch-clamp monitoring of Ca2+-dependent ionic currents [6-8]. Picomolar concentrations of bombesin and CCK evoked similar patterns of cytosolic Ca2+ oscillations, but high, desensitising, NAADP concentrations selectively inhibited CCK, but not bombesin-evoked signals. Inhibiting inositol trisphosphate (IP3) receptors with a high concentration of caffeine blocked both types of oscillations. We further tested whether NAADP is involved in Ca2+ signals triggered by activation of the low-affinity CCK receptor sites. Nanomolar concentrations of CCK evoked non-oscillatory Ca2+ signals, which were not affected by desensitising NAADP receptors. Our results suggest that Ca2+-release channels gated by the novel Ca2+-mobilising molecule NAADP are only essential in specific Ca2+-mobilising pathways, whereas the IP3 receptors are generally required for Ca2+ signals. Thus, the same cell may use different combinations of intracellular Ca2+-releasing messengers to encode different external messages. |
spellingShingle | Burdakov, D Galione, A Two neuropeptides recruit different messenger pathways to evoke Ca2+ signals in the same cell. |
title | Two neuropeptides recruit different messenger pathways to evoke Ca2+ signals in the same cell. |
title_full | Two neuropeptides recruit different messenger pathways to evoke Ca2+ signals in the same cell. |
title_fullStr | Two neuropeptides recruit different messenger pathways to evoke Ca2+ signals in the same cell. |
title_full_unstemmed | Two neuropeptides recruit different messenger pathways to evoke Ca2+ signals in the same cell. |
title_short | Two neuropeptides recruit different messenger pathways to evoke Ca2+ signals in the same cell. |
title_sort | two neuropeptides recruit different messenger pathways to evoke ca2 signals in the same cell |
work_keys_str_mv | AT burdakovd twoneuropeptidesrecruitdifferentmessengerpathwaystoevokeca2signalsinthesamecell AT galionea twoneuropeptidesrecruitdifferentmessengerpathwaystoevokeca2signalsinthesamecell |