Brimijoin S, Dagerlind A, Rao R, McKinzie S, Hammond P
Department of Pharmacology, Mayo Clinic, Rochester, Minnesota 55905.
J Neurochem. 1995 Mar;64(3):1281-7. doi: 10.1046/j.1471-4159.1995.64031281.x.
To investigate transsynaptic effects on peptides of adrenal chromaffin cells in the rat, presynaptic sympathetic terminals were destroyed by intravenous injection of monoclonal antibodies to acetylcholinesterase. At several times thereafter, neuropeptide Y (NPY)-like immunoreactivity (NPY-IR) and methionine-enkephalin-like immunoreactivity (Met-Enk-IR) were measured by radioimmunoassay. Within 2 days of antibody injection, adrenal Met-Enk-IR increased five- to 10-fold and NPY-IR increased 50%. These effects were accompanied by large increases in proenkephalin A mRNA assayed by polymerase chain reaction. The peptide responses could reflect either an acute activation, as presynaptic terminals degenerated, or a chronic synaptic inactivation after terminal degeneration. To test the possibilities, muscarinic and nicotinic receptors were inhibited by repeated injection of atropine (1 mg/kg) and chlorisondamine (5 mg/kg). Measurements of urinary free catecholamine excretion showed that this treatment prevented the paroxysmal release of norepinephrine and reduced the release of epinephrine that normally followed injection of acetylcholinesterase antibodies. When the drugs were given alone for 2 or 4 days, adrenal Met-Enk-IR increased modestly and NPY-IR remained steady or declined. When given together with acetylcholinesterase antibodies, the cholinergic antagonists blocked the increase of NPY-IR but not Met-Enk-IR. Adding naloxone (1 mg/kg) to the treatment regimen enhanced the blockade of epinephrine excretion and largely prevented the antibody-induced increase in Met-EnK-IR. These findings indicate that adrenal NPY and enkephalin are not regulated identically. Adrenal NPY behaves as though controlled by transsynaptic cholinergic input. On the other hand, adrenal enkephalin may be regulated by additional or different mechanisms, possibly involving peptidergic transmission or synaptic inactivation.
为研究对大鼠肾上腺嗜铬细胞肽类的跨突触效应，通过静脉注射抗乙酰胆碱酯酶单克隆抗体破坏突触前交感神经末梢。此后在几个时间点，采用放射免疫分析法测定神经肽Y（NPY）样免疫反应性（NPY-IR）和甲硫氨酸脑啡肽样免疫反应性（Met-Enk-IR）。抗体注射后2天内，肾上腺Met-Enk-IR增加了5至10倍，NPY-IR增加了50%。这些效应伴随着通过聚合酶链反应检测的前脑啡肽A mRNA的大幅增加。肽类反应可能反映突触前末梢退化时的急性激活，或末梢退化后的慢性突触失活。为验证这些可能性，通过反复注射阿托品（1mg/kg）和氯异吲哚铵（5mg/kg）抑制毒蕈碱和烟碱受体。尿游离儿茶酚胺排泄量的测量表明，这种治疗可防止去甲肾上腺素的阵发性释放，并减少通常在注射乙酰胆碱酯酶抗体后出现的肾上腺素释放。当单独给予这些药物2或4天时，肾上腺Met-Enk-IR适度增加，NPY-IR保持稳定或下降。当与乙酰胆碱酯酶抗体一起给予时，胆碱能拮抗剂阻断了NPY-IR的增加，但未阻断Met-Enk-IR的增加。在治疗方案中加入纳洛酮（1mg/kg）可增强对肾上腺素排泄的阻断作用，并在很大程度上防止抗体诱导的Met-EnK-IR增加。这些发现表明，肾上腺NPY和脑啡肽的调节方式不同。肾上腺NPY的行为似乎受跨突触胆碱能输入的控制。另一方面，肾上腺脑啡肽可能受其他或不同机制的调节，可能涉及肽能传递或突触失活。
