Modulation by adenosine of both muscarinic M1-facilitation and M2-inhibition of [3H]-acetylcholine release from the rat motor nerve terminals
Modulation by adenosine of both muscarinic M1-facilitation and M2-inhibition of [3H]-acetylcholine release from the rat motor nerve terminals
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DOI：
10.1046/j.1460-9568.2002.02020.x
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发表时间：
2002-06-01
影响因子：
3.4
通讯作者：
Correia-de-Sá, P
中科院分区：
文献类型：
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作者：
Oliveira, L;Timóteo, MA;Correia-de-Sá, P
研究了大鼠膈神经-膈膜制剂诱导[(3)H]-乙酰胆碱（[(3)H]-乙酰胆碱）释放时腺苷与毒碱碱自受体之间的串音。运动神经末梢具有促进性M-1和抑制性M-2自受体，分别可被McN-A-343 （1-30 μ m）和氧tremorine （0.3-100 μ m）激活。毒蕈碱受体拮抗剂双环胺（3 nm-10 mum）引起双相（抑制/促进）效应，表明在5hz刺激序列中M-1 -促进作用占优势。与M-1拮抗剂毒蕈碱毒素7 （MT-7, 0.1 nm）和吡renzepine （1 nm）预处理后，AF-DX 116敏感的M-2受体的同时激活部分减弱，显著增强了氧tremorine的抑制作用。CGS 21680C （2nm）激活A(2A) -腺苷受体(i)增强了氧tremorine的抑制作用，（ii）将mcn -A-343诱导的促进作用转变为小的抑制作用。相反，A(1)受体激动剂R-N(6) -苯异丙基腺苷（R-PIA, 100 nm）减弱了氧tremorine的抑制作用，但不改变McN-A-343的促进作用。A（2A）和M-2受体之间的协同作用是通过与促进性M-1受体的相互作用来调节的，这种相互作用可能被吡仑西平（1nm）阻止。在50 hz -burst期间，McN-A-343对[(3)H]-ACh释放的促进作用（M-1）消失，而氧tremorine的抑制作用（M-2）起主导作用。由于选择性A（2A）受体拮抗剂ZM 241385 （10 nm）阻止了与A（2A）受体的相互作用，因此这种毒蕈碱性转变是由A（2A）受体相互作用引起的。综上所述，当毒蕈碱M-1正反馈回路完全发挥作用时，腺苷A(1)受体介导了ACh释放的负调控。在高频爆发期间，A（2A）受体的强直激活通过抑制M-1受体操作的反作用力来促进M-2的自抑制。
The crosstalk between adenosine and muscarinic autoreceptors regulating evoked [(3) H]-acetylcholine ([(3) H]-ACh) release was investigated on rat phrenic nerve-hemidiaphragm preparations. Motor nerve terminals possess facilitatory M-1 and inhibitory M-2 autoreceptors that can be activated by McN-A-343 (1-30 mum) and oxotremorine (0.3-100 mum), respectively. The muscarinic receptor antagonist, dicyclomine (3 nm-10 mum), caused a biphasic (inhibitory/facilitatory) effect, indicating that M-1 -facilitation prevails during 5 Hz stimulation trains. Concomitant activation of AF-DX 116-sensitive M-2 receptors was partially attenuated, as pretreatment with M-1 antagonists, muscarinic toxin 7 (MT-7, 0.1 nm) and pirenzepine (1 nm), significantly enhanced inhibition by oxotremorine. Activation of A(2A) -adenosine receptors with CGS 21680C (2 nm) (i) potentiated oxotremorine inhibition, and (ii) shifted McN-A-343-induced facilitation into a small inhibitory effect. Conversely, the A(1) -receptor agonist, R-N (6) -phenylisopropyl adenosine (R-PIA, 100 nm), attenuated the inhibitory effect of oxotremorine, without changing facilitation by McN-A-343. Synergism between A(2A) and M-2 receptors is regulated by a reciprocal interaction with facilitatory M-1 receptors, which may be prevented by pirenzepine (1 nm). During 50 Hz-bursts, facilitation (M-1 ) of [(3) H]-ACh release by McN-A-343 disappeared, while the inhibitory (M-2 ) effect of oxotremorine became predominant. This muscarinic shift results from the interplay with A(2A) receptors, as it was precluded by the selective A(2A) receptor antagonist, ZM 241385 (10 nm). In conclusion, when the muscarinic M-1 positive feedback loop is fully operative, negative regulation of ACh release is mediated by adenosine A(1) receptors. During high frequency bursts, tonic activation of A(2A) receptors promotes M-2 autoinhibition by braking the M-1 receptor operated counteraction.