Cecilia Cremer M, Silvina Sanchez M, Ester Celis M
Laboratorio de Fisiología, Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, CP 5000, Córdoba, Argentina.
Peptides. 2000 Jun;21(6):803-6. doi: 10.1016/s0196-9781(00)00211-4.
In this work, we characterized the active site in the alpha-melanotropin hormone (alpha-MSH) sequence responsible for the enhancement of cAMP production in incubated striatal slices by using different alpha-MSH fragments. We also analyzed the effects of the co-incubation of the SCH23390, a dopaminergic D(1) antagonist, with the MSH fragments, to study the involvement of the D(1) receptor on this induction. A rise was observed in the levels of cAMP after addition of the 6 microM fragments MSH((1-10)), and 0.6 and 6 microM MSH((5-13)); however, the values were lower than those induced by 6 microM alpha-MSH. On the contrary, the addition of MSH((9-13)), MSH((7-11)), or MSH((6-9)) did not affect the cAMP content. The presence of 10 microM SCH23390 blocked the effect of the fragments on cAMP production. We conclude that the biologic activity of alpha-MSH, as observed through the levels of cAMP, declines when the length of its polypeptide chain is shortened, and that the presence of glutamic acid in the molecule, as well as the core sequence, are of importance for fragments' activity.
在本研究中，我们通过使用不同的α-促黑素（α-MSH）片段，对α-促黑素激素（α-MSH）序列中负责增强孵育纹状体切片中环磷酸腺苷（cAMP）生成的活性位点进行了表征。我们还分析了多巴胺能D(1)拮抗剂SCH23390与MSH片段共同孵育的效果，以研究D(1)受体在此诱导过程中的作用。添加6微摩尔片段MSH((1-10))、0.6微摩尔和6微摩尔MSH((5-13))后，观察到cAMP水平升高；然而，这些值低于6微摩尔α-MSH诱导的值。相反，添加MSH((9-13))、MSH((7-11))或MSH((6-9))对cAMP含量没有影响。10微摩尔SCH23390的存在阻断了片段对cAMP生成的作用。我们得出结论，通过cAMP水平观察到的α-MSH的生物活性在其多肽链长度缩短时会下降，并且分子中谷氨酸的存在以及核心序列对片段的活性很重要。
