Florijn W J, Mulder A H, Versteeg D H, Gispen W H
Department of Pharmacology, Rudolf Magnus Institute, Medical Faculty, University of Utrecht, The Netherlands.
J Neurochem. 1993 Jun;60(6):2204-11. doi: 10.1111/j.1471-4159.1993.tb03506.x.
The regulation of adenylate cyclase activity by adrenocorticotropin/alpha-melanocyte-stimulating hormone (ACTH/MSH)-like peptides was investigated in rat brain slices using a superfusion method. Adenylate cyclase activity was concentration-dependently increased by ACTH-(1-24), alpha-MSH (EC50 values 16 and 6 nM, respectively), and [Nle4,D-Phe7]alpha-MSH (EC50 value 1.6 nM), in the presence of forskolin (1 microM, optimal concentration). 1-9-Dideoxyforskolin did not augment the response of adenylate cyclase to ACTH-(1-24). Various peptide fragments were tested for their ability to enhance [3H]cyclic AMP production. [Nle4,D-Phe7]alpha-MSH increased [3H]cyclic AMP formation with a maximal effect of 30% and was more potent than ACTH-(1-24), ACTH-(1-16)-NH2, alpha-MSH, ACTH-(1-13)-NH2, [MetO4]alpha-MSH, [MetO2(4),D-Lys8,Phe9]ACTH-(4-9), ACTH-(7-16)-NH2, ACTH-(1-10), and ACTH-(11-24), in order of potency. This structure-activity relationship resembles that found for the previously described peptide-induced display of excessive grooming. ACTH-(1-24) stimulated adenylate cyclase activity in both striatal (maximal effect, approximately 20%) and septal slices (maximal effect, approximately 40%), but not in hippocampal or cortical slices. Lesioning of the dopaminergic projections to the striatum did not result in a diminished effect of [Nle4,D-Phe7]alpha-MSH on [3H]cyclic AMP accumulation, which indicates that the ACTH/MSH receptor-stimulated adenylate cyclase is not located on striatal dopaminergic terminals. ACTH-(1-24) did not affect the dopamine D1 or D2 receptor-mediated modulation of adenylate cyclase activity.(ABSTRACT TRUNCATED AT 250 WORDS)
采用灌流法在大鼠脑片中研究促肾上腺皮质激素/α-黑素细胞刺激素（ACTH/MSH）样肽对腺苷酸环化酶活性的调节作用。在存在福斯高林（1μM，最佳浓度）的情况下，ACTH-(1-24)、α-MSH（EC50值分别为16和6 nM）和[Nle4,D-Phe7]α-MSH（EC50值为1.6 nM）可使腺苷酸环化酶活性呈浓度依赖性增加。1-9-二脱氧福斯高林不会增强腺苷酸环化酶对ACTH-(1-24)的反应。测试了各种肽片段增强[3H]环磷酸腺苷生成的能力。[Nle4,D-Phe7]α-MSH使[3H]环磷酸腺苷形成增加，最大效应为30%，且比ACTH-(1-24)、ACTH-(1-16)-NH2、α-MSH、ACTH-(1-13)-NH2、[MetO4]α-MSH、[MetO2(4),D-Lys8,Phe9]ACTH-(4-9)、ACTH-(7-16)-NH2、ACTH-(1-10)和ACTH-(11-24)更有效，按效力顺序排列。这种构效关系类似于先前描述的肽诱导过度梳理行为的情况。ACTH-(1-24)刺激纹状体切片（最大效应约20%）和隔区切片（最大效应约40%）中的腺苷酸环化酶活性，但不刺激海马或皮质切片中的活性。损毁投射到纹状体的多巴胺能神经纤维不会导致[Nle4,D-Phe7]α-MSH对[3H]环磷酸腺苷积累的作用减弱，这表明ACTH/MSH受体刺激的腺苷酸环化酶不在纹状体多巴胺能终末上。ACTH-(1-24)不影响多巴胺D1或D2受体介导的腺苷酸环化酶活性调节。（摘要截短至250字）
