ACTH-(4-10) through gamma-MSH: evidence for a new class of central autonomic nervous system-regulating peptides.
ACTH-(4-10) through gamma-MSH: evidence for a new class of central autonomic nervous system-regulating peptides.
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ACTH-(4-10) 至 γ-MSH：一类新型中枢自主神经系统调节肽的证据。
DOI：
10.1152/ajpregu.1989.257.4.r681
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Callahan,MF
中科院分区：
文献类型：
--
作者：
Gruber,KA;Callahan,MF
通过对外周施用促肾上腺皮质激素 (ACTH) 衍生的肽序列产生的心血管效应的检查，发现了静脉注射 (iv) ACTH-(4-10) 的升压、心脏加速和利尿钠作用。根据对α-和β-肾上腺素能受体拮抗剂的大鼠进行的药理学研究，该肽的心血管作用似乎是通过儿茶酚胺的释放介导的。与 ACTH-(4-10)、γ-黑素细胞刺激激素 (γ-MSH) 类似的肽序列，其心血管活性比 ACTH-(4-10) 高 100 倍以上，而利尿钠活性高 1,000 倍以上。静脉注射γ-MSH肽的升压作用似乎依赖于节前交感神经驱动的维持，而循环加压素或血管紧张素II没有显着贡献。然而，中枢血管加压素能途径，或许还有血管紧张素能途径的存在似乎对于循环γ-MSH的完全升压作用的表达至关重要。通过中枢病变实验以及颈动脉内输注与颈内输注的比较，获得了中枢神经系统 (CNS) 在这些心血管影响中的潜在重要性的进一步证据。结构-活性研究表明，ACTH-(4-10) 或 γ-MSH 的心血管作用取决于位于或靠近其 COOH 末端的 Arg 疏水氨基酸序列。在软体动物心脏兴奋肽中也发现了类似的生物活性要求，并且软体动物肽对大鼠具有心血管作用，类似于ACTH-(4-10)或γ-MSH。这表明γ-MSH家族的肽是软体动物和鸟类中发现的心脏兴奋肽家族的药理学类似物，并且可能是生理同源物。研究发现，在心理压力、心血管窘迫和出血中，源自阿片黑皮素原 (POMC) NH2 末端的肽的循环水平升高。中枢交感神经冲动的增强是所有这些状态的共同点。 γ-MSH 肽已定位于大鼠弓状核和连合核的 POMC 神经元。后一个核的投射支配后脑血管运动中心。脑室内注射 γ-MSH 可使平均动脉压持续升高。 γ-MSH 肽可能在心血管调节中提供体液和神经源性机制之间的联系，并且可能是心血管系统中枢控制的重要神经递质。
Examination of the cardiovascular effects produced by peripheral administration of peptide sequences derived from adrenocorticotropic hormone (ACTH) led to the discovery of the pressor, cardioaccelerator, and natriuretic actions of intravenous (iv) ACTH-(4-10). Based on pharmacological studies in rats with alpha- and beta-adrenergic receptor antagonists, the cardiovascular effects of this peptide appeared to be mediated by the release of catecholamines. A peptide sequence analogous to ACTH-(4-10), gamma-melanocyte-stimulating hormone (gamma-MSH), possesses greater than 100-fold more cardiovascular activity and 1,000-fold more natriuretic activity than ACTH-(4-10). The pressor effect of iv gamma-MSH peptides appears to be dependent on the maintenance of preganglionic sympathetic drive, with no significant contribution of circulating vasopressin or angiotensin II. However, the presence of central vasopressinergic, and perhaps angiotensinergic, pathways appears to be crucial for expression of the full pressor effect of circulating gamma-MSH. Further evidence for the potential importance of the central nervous system (CNS) in these cardiovascular effects was obtained from central lesion experiments and a comparison of intracarotid vs. intrajugular infusions. Structure-activity studies suggested that the cardiovascular effects of ACTH-(4-10) or gamma-MSH are dependent on an Arg-hydrophobic amino acid sequence, located at or near their COOH-terminal. A similar requirement for biological activity is found in molluscan cardioexcitatory peptides, and the molluscan peptides have cardiovascular effects in rats, which resemble ACTH-(4-10) or gamma-MSH. This suggests that peptides of the gamma-MSH family are the pharmacological analogues, and perhaps the physiological homologues, of a cardioexcitatory family of peptides found in molluscs and birds. Elevated circulating levels of peptides derived from the NH2-terminal of pro-opiomelanocortin (POMC) have been found in psychological stress, cardiovascular distress, and hemorrhage. Increases in central sympathetic drive are common to all of these states. gamma-MSH peptides have been localized to POMC neurons in the arcuate nucleus and nucleus commissuralis of the rat. Projections from the latter nucleus innervate hindbrain vasomotor centers. Intraventricular administration of gamma-MSH produces prolonged elevation of mean arterial pressure. gamma-MSH peptides may provide a link between humoral and neurogenic mechanisms in cardiovascular regulation and could potentially be important neurotransmitters for central control of the cardiovascular system.