Mota Alberto, Guimarães Serafim
Instituto de Farmacologia e Terapêutica, Faculdade de Medicina do Porto, Alameda Prof. Hernâni Monteiro, 4200-319, Porto, Portugal.
Naunyn Schmiedebergs Arch Pharmacol. 2003 Dec;368(6):443-7. doi: 10.1007/s00210-003-0840-2. Epub 2003 Nov 26.
The interaction between alpha(2)-autoreceptors and receptors for angiotensin II and bradykinin was studied in the heart of newborn rats. The tissues were labeled with [3H] noradrenaline and then superfused with cocaine-containing medium and stimulated electrically. Angiotensin II (30-1,000 nM) and bradykinin (10-300 nM) enhanced the evoked overflow of tritium, the maximum increase reaching 52.2 and 72.8%, respectively. In the presence of the selective alpha(2)-adrenoceptor agonist UK-14,304, the maximal effect caused by angiotensin II and bradykinin was enhanced reaching 92.1 and 87.1% for angiotensin II and bradykinin, respectively. On the contrary, in the presence of chelerythrine (a protein kinase C blocker), not only the increment in facilitation by UK-14,304, but to some extent also the basal facilitation caused by angiotensin II and bradykinin were markedly reduced (to 17.3 and 43.2%, respectively). We conclude that: 1. The stimulation of alpha2-autoreceptors enhances the facilitatory responses caused by angiotensin II and bradykinin, confirming that an ongoing alpha2-autoinhibition is required for the facilitatory influence of the peptides. 2. Protein kinase C is involved in the enhancement by angiotensin II and bradykinin of electrically-evoked release of noradrenaline from the nerve terminals.
在新生大鼠心脏中研究了α₂ - 自身受体与血管紧张素II和缓激肽受体之间的相互作用。用[³H]去甲肾上腺素标记组织，然后用含可卡因的培养基进行灌流并电刺激。血管紧张素II（30 - 1000 nM）和缓激肽（10 - 300 nM）增强了诱发的氚溢出，最大增加分别达到52.2%和72.8%。在选择性α₂ - 肾上腺素能受体激动剂UK - 14,304存在的情况下，血管紧张素II和缓激肽引起的最大效应增强，血管紧张素II和缓激肽分别达到92.1%和87.1%。相反，在白屈菜红碱（一种蛋白激酶C阻滞剂）存在的情况下，不仅UK - 14,304诱导的促进作用增加受到抑制，而且血管紧张素II和缓激肽引起的基础促进作用在一定程度上也显著降低（分别降至17.3%和43.2%）。我们得出以下结论：1. 刺激α₂ - 自身受体增强了血管紧张素II和缓激肽引起的促进反应，证实这些肽的促进作用需要持续的α₂ - 自身抑制。2. 蛋白激酶C参与了血管紧张素II和缓激肽增强神经末梢去甲肾上腺素电诱发释放的过程。
