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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Sugden, D. |
| Description | Author Affiliation: Sugden D ( Biomedical Sciences Division, King's College London.) |
| Abstract | 1. Isolated melanophores were differentiated from aggregates of neural crest obtained from neurula stage Xenopus laevis embryos after 2 days in culture. 2. Condensation of pigment granules in these cells by melatonin (5-methoxy N-acetyltryptamine, aMT) and various novel analogues was monitored with an image analysis system to quantitate the area occupied by pigment in individual cells. 3. Melanophores exposed to vehicle (a maximum of 0.1% MeOH) showed little (less than 5%) change in pigment area. aMT produced a dramatic condensation of pigment granules (EC50 = the concentration producing a half maximal condensation, 9 pM). The response was rapid, reached a maximum (approximately 80% decrease in pigmented area) by 10 min, and was reversible after removal of aMT from the culture medium. 4. Aggregation to aMT was blocked by treating melanophores with pertussis toxin (1 microgram ml-1, 7 h) indicating a role for a guanosine 5' triphosphate (GTP)-binding protein in transducing the aMT receptor signal. 5. Structure-activity studies indicated that analogues of aMT lacking a side-chain N-acyl substituent (5-methoxytryptamine, MT) or a group at the 5-position of the indole ring (N-acetyltryptamine, aT) were unable to induce pigment aggregation (EC50 greater than 10 microM). 6. Lengthening the side-chain N-acyl group (N-propionyl, N-butanoyl) was tolerated to some degree but eventually (N-valeroyl and larger) activity diminished. Of the 5-position analogues tested 5-methoxy (aMT) was by far the most potent. 7. Halogen substitution in the 6-position of the indole ring led to some loss of activity as did a 6-OH substitution. The 6-OCH3 compound was inactive.8. These studies demonstrate the utility of this model in investigations of structure-activity relationships at the aMT receptor and suggest that it may be a valuable system for determining the transduction mechanisms coupled to the aMT receptor. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 4 |
| Volume Number | 104 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1991-12-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Cytoplasmic Granules Drug Effects Melanophores Melatonin Pharmacology Pigments, Biological Physiology Animals Calcium Embryo, Nonmammalian Cytology GTP-Binding Proteins Metabolism Ultrastructure Analogs & Derivatives Neural Crest Pertussis Toxin Receptors, Melatonin Receptors, Neurotransmitter Signal Transduction Structure-Activity Relationship Virulence Factors, Bordetella Xenopus Laevis |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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