Novales R R
J Invest Dermatol. 1977 Nov;69(5):446-50. doi: 10.1111/1523-1747.ep12511041.
Calcium ions are required in the medium for the full darkening action of melanocyte-stimulating hormone, but not for its second messenger, cyclic adenosine monophosphate, on isolated frog skin. Thus, the possible effect of the divalent cation ionophore A23187 was studied, using the skin of Rana pipiens. It is a potent darkening agent over the range of 1-2 micrometer, as measured by reflectance change and microscopic observation. During the darkening response of A23187, melanosome dispersion takes place in both dermal and epidermal melanophores, as well as aggregation of iridophore reflecting platelets. The darkening is slowly reversible in Ringer's solution, thus it is not due to toxicity. The darkening is partially dependent on the presence of calcium in the medium under certain conditions, suggesting that the response involves both the uptake and release of calcium ions. Cytochalasin B reversibly inhibits the darkening produced by A23187. Since this drug is known to bring about the breakdown of microfilaments, its inhibitory action is in accord with the concept that the ionophore is stimulating microfilament function. A23187 administered to tissue cultured embryonic salamander (Ambystoma maculatum) melanophores produced an irreversible rounding up of the cells, suggesting a toxic effect. The results with frog skin are interpreted as supporting the concept that the action of melanocyte-stimulating hormone involves the production of pigment granule movements as a result of the interaction of calcium ions with intracellular microfilaments and possible also the breakdown of microtubules. The mobilization of calcium ions could be brought about by cyclic adenosine monophosphate.
培养基中需要钙离子才能使促黑素细胞激素发挥完全的变黑作用,但对于其第二信使环磷酸腺苷在离体蛙皮上的作用而言则不需要。因此,使用豹蛙皮肤研究了二价阳离子载体A23187可能产生的作用。通过反射率变化和显微镜观察测量,它在1 - 2微米范围内是一种有效的变黑剂。在A23187引起的变黑反应过程中,真皮和表皮黑素细胞中都会发生黑素体分散,同时虹彩细胞反射小板会聚集。在林格氏液中,变黑反应是缓慢可逆的,因此这不是由毒性引起的。在某些条件下,变黑反应部分依赖于培养基中钙离子的存在,这表明该反应涉及钙离子的摄取和释放。细胞松弛素B可可逆地抑制A23187产生的变黑反应。由于已知这种药物会导致微丝断裂,其抑制作用与离子载体刺激微丝功能的概念相符。将A23187施用于组织培养的胚胎蝾螈(美西螈)黑素细胞会导致细胞不可逆地变圆,表明存在毒性作用。对蛙皮的研究结果被解释为支持这样一种观点,即促黑素细胞激素的作用涉及由于钙离子与细胞内微丝相互作用以及可能还有微管的断裂而产生色素颗粒运动。钙离子的动员可能是由环磷酸腺苷引起的。