Melatonin Modulation In Innervated Melanophores

With the two-site receptor model in mind, we suggest a new possibility: melatonin may modulate the a2-adrenoceptor response (4). This hypothesis implies that a hormone and a neurotransmitter can somehow integrate their own signal messengers into a common signal. The question is where does the interaction occur? Does it take place on the receptor surface and involve an allosteric site, or does it occur somewhere along the transduction pathway, or at some point during the intracellular process that controls pigment aggregation?

Melatonin alone has almost no effect on pigment aggregation in melanophores on isolated scales, but it did enhance pigment aggregation that had been elicited via the a2-adrenoceptor. Thus, the effect of melatonin must be dependent on the presence of an a2-adrenoceptor (Figure 3). However, melatonin had the opposite effect when used in combination with B-HT 920 which is another a2-adrenoceptor agonist (Figure 4). Instead of increasing aggregation as with the other a2-adrenoceptor agonists, melatonin counteracts the aggregation induced by B-HT 920. A possible hypothesis for the counteracting effect seen with melatonin against B-HT 920 could be that those two substances bind to the same site, a site different from the catecholamine binding site, but with different affinity and efficacy. That is, if melatonin binds with a higher affinity

Figure 3. The combined effect of melatonin and noradrenaline (NA) on pigment aggregation in fish melanophores. The pigment granules were partially aggregated by exposure to various concentrations of noradrenaline and the melanophores were subsequently exposed to different concentrations of melatonin (as indicated on the x axis). Symbols: control, i.e. melatonin only (•), n = 10; melatonin and 0.1 mM NA (♦), n = 5; melatonin and 1mM NA (H)n = 15; melatonin and 10 mM NA (•), n = 10. Each point in the graph represents the mean ± SEM. The statistics were elucidated by Wilcoxon signed-rank test between the NA points, as indicated on the x-axis, and increasing doses of melatonin. The significance levels were set at 95% (*), 99% (**) and 99.9% (***). (With kind permission from Elsevier, ref 8).

Wilcoxon Signed Rank Symbols Images

Figure 3. The combined effect of melatonin and noradrenaline (NA) on pigment aggregation in fish melanophores. The pigment granules were partially aggregated by exposure to various concentrations of noradrenaline and the melanophores were subsequently exposed to different concentrations of melatonin (as indicated on the x axis). Symbols: control, i.e. melatonin only (•), n = 10; melatonin and 0.1 mM NA (♦), n = 5; melatonin and 1mM NA (H)n = 15; melatonin and 10 mM NA (•), n = 10. Each point in the graph represents the mean ± SEM. The statistics were elucidated by Wilcoxon signed-rank test between the NA points, as indicated on the x-axis, and increasing doses of melatonin. The significance levels were set at 95% (*), 99% (**) and 99.9% (***). (With kind permission from Elsevier, ref 8).

log Melatonin [M]

Figure 4. The combined effect of melatonin and B-HT 920 on pigment aggregation in fish melanophores. The pigment granules were partially aggregated by exposure to 10 mM B-HT 920 (BT), n = 15, and the melanophores were subsequently exposed to different concentrations of melatonin, as indicated on the x-axis. (With kind permission from Elsevier, ref 8).

Figure 4. The combined effect of melatonin and B-HT 920 on pigment aggregation in fish melanophores. The pigment granules were partially aggregated by exposure to 10 mM B-HT 920 (BT), n = 15, and the melanophores were subsequently exposed to different concentrations of melatonin, as indicated on the x-axis. (With kind permission from Elsevier, ref 8).

but less efficacy than B-HT 920 does, and when the two drugs are combined, if the one with higher affinity, i.e. melatonin, occupies the binding site more often or more strongly, the overall result will be an inhibition of aggregation. On the other hand, if melatonin is combined with noradrenaline, two sites will be occupied resulting in a syn-ergistic effect, possibly through potentiation of the signal transduction pathway. However, the hypothesis presented above is at odds with the common opinion on how melatonin interacts with receptors, but in our opinion, this is one possibility to interpret the pharmacological results.

Super Serenity Sleepers

Super Serenity Sleepers

Do You Have Problem Getting A Good Night Sleep? Learn To Sleep Like A Cat At Night And Run Like A Lion When You Wake Up.

Get My Free Ebook


Post a comment