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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Yang, C. M. Luo, S. F. Hsieh, J. T. Ong, R. Hsia, H. C. |
| Description | Author Affiliation: Yang CM ( Department of Pharmacology, Chang Gung Medical College, Kwei-San, Tao-Yuan, Taiwan.) |
| Abstract | 1. The effects of cholera toxin (CTX), forskolin and dibutyryl cyclic AMP on bradykinin (BK)- and carbachol-induced accumulation of inositol phosphates (IPs) and Ca2+ mobilization were investigated in canine cultured tracheal smooth muscle cells (TSMCs). The BK-induced responses were mediated via a G protein which was not inhibited by CTX or pertussis toxin treatment. 2. BK-stimulated IPs accumulation and Ca2+ mobilization were potentiated by CTX (10 micrograms ml-1) pretreatment which was time-dependent. Maximal increase of these responses occurred after 24 h treatment with CTX. The concentration-effect relationship of BK-induced responses were shifted to the left and BK was substantially more effective in CTX-treated cells than in the control cells. This enhancing effect of CTX did not occur with carbachol. 3. Short-term (< 4 h) treatment with forskolin (10 microM) or dibutyryl cyclic AMP (1 mM) failed to accentuate BK-induced responses, but long-term (> 4 h) treatment of TSMCs with these agents mimicked the enhancing effect of CTX, suggesting that CTX-induced enhancement of BK responsiveness might be due to a rise in cyclic AMP. 4. Prolonged treatment of TSMCs with these agents was accompanied by an increase in cell surface [3H]-BK binding sites, which was inhibited by concurrent incubation with cycloheximide, an inhibitor of protein biosynthesis. Cycloheximide also abolished the potentiating actions of CTX, forskolin, and dibutyryl cyclic AMP on BK-induced IPs formation and Ca2+ mobilization. 5. The locus of this enhancement was further investigated by examining the effects of CTX, forskolin and dibutyryl cyclic AMP on A1F4(-)-induced IPs accumulation in canine TSMCs. AIF4-induced IPs accumulation was not affected by CTX, forskolin, or dibutyryl cyclic AMP treatment, supporting the contention that this stimulatory effect is located at the BK receptor level.6. These results demonstrate that the augmentation of BK-induced IPs accumulation and Ca2+mobilization produced by CTX, forskolin and dibutyryl cyclic AMP involves a cyclic AMP-dependent mechanism which is induced by a sustained increase in the level of intracellular cyclic AMP. CTX and forskolin may promote an increase of the synthesis of BK receptors, and thereby enhance BK-induced responses. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 3 |
| Volume Number | 112 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1994-07-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Bradykinin Pharmacology Carbachol Cyclic AMP Biosynthesis Muscle, Smooth Drug Effects Signal Transduction Trachea Animals Metabolism Bucladesine Calcium Cells, Cultured Cholera Toxin Colforsin Cycloheximide GTP-Binding Proteins Inositol Phosphates Cytology Receptors, Bradykinin Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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