Abstract |
1. Measurement of [Ca2+]i in single rat pituitary GH3 cells by dynamic single cell imaging techniques demonstrated that under basal conditions there is a large variation in the temporal pattern of [Ca2+]i signalling between individual cells ranging from high frequency asynchronous oscillations to quiescence. 2. We have reported previously that treatment of GH3 cells with 1 mM Li+ (a concentration used therapeutically in the treatment of manic depression) for 7 days reduces basal and thyrotrophin-releasing hormone (TRH)-stimulated levels of mass inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]. In the present study, we show that this is associated with a reduction in the number of cells exhibiting basal Ca2+ oscillations over a sampling period of 60 s, whereas the maximum amplitude of oscillations is unaffected. 3. The pattern of [Ca2+]i responses to the agonist TRH varied considerably between individual cells, making quantitation of the responses difficult; however, data obtained from measurements made on a population of cells showed that increases in peak [Ca2+]i induced by high concentrations of TRH were reduced in cells treated with 1 mM Li+ for 7 days relative to control cells. 4. The sensitivity of the phosphoinositide pathway to [Ca2+]i was investigated by loading GH3 cells with BAPTA/AM at a concentration sufficient to lower 'basal' [Ca2+]i in a population of cells and to inhibit agonist-stimulated increases in [Ca2+]i. Under these conditions, basal and TRH-stimulated mass Ins(1,4,5)P3 levels were unaffected. 5. These results demonstrate that a 7-day Li+ treatment leads to an alteration in Ca2+ signalling, in particular by reducing the number of cells exhibiting high frequency Ca2+ oscillations under basal conditions. The significance of these results to the clinical effectiveness of Li+ in the treatment of manic depression is discussed.
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Authors | M A Varney, A Galione, S P Watson |
Journal | British journal of pharmacology
(Br J Pharmacol)
Vol. 112
Issue 2
Pg. 390-5
(Jun 1994)
ISSN: 0007-1188 [Print] England |
PMID | 8075856
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Egtazic Acid
- Thyrotropin-Releasing Hormone
- Inositol 1,4,5-Trisphosphate
- Prolactin
- Lithium
- 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
- Calcium
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Topics |
- Animals
- Calcium
(metabolism)
- Cell Line
- Egtazic Acid
(analogs & derivatives, pharmacology)
- Image Processing, Computer-Assisted
- Inositol 1,4,5-Trisphosphate
(metabolism)
- Lithium
(pharmacology)
- Pituitary Gland
(cytology, drug effects, metabolism)
- Prolactin
(metabolism)
- Rats
- Thyrotropin-Releasing Hormone
(pharmacology)
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