INHIBITION BY OPIOIDS ACTING ON MU-RECEPTORS OF GABAERGIC AND GLUTAMATERGIC POSTSYNAPTIC POTENTIALS IN SINGLE-RAT PERIAQUEDUCTAL GRAY NEURONS IN-VITRO
INHIBITION BY OPIOIDS ACTING ON MU-RECEPTORS OF GABAERGIC AND GLUTAMATERGIC POSTSYNAPTIC POTENTIALS IN SINGLE-RAT PERIAQUEDUCTAL GRAY NEURONS IN-VITRO
复制标题
DOI：
10.1111/j.1476-5381.1994.tb16209.x
复制
发表时间：
1994-09-01
影响因子：
7.3
通讯作者：
CHRISTIE, MJ
中科院分区：
文献类型：
--
作者：
CHIENG, B;CHRISTIE, MJ
1 通过使用脑切片中单个神经元的细胞内记录来研究大鼠导水管周围灰色神经元的膜特性。通过用生物胞素进行细胞内染色来表征每个刺穿神经元的形态特性和解剖位置。本文考虑了影响导水管周围灰色神经元的电诱发和自发突触后电位的特性，以及阿片类药物对未直接被阿片类药物超极化的神经元突触后电位的作用。前一篇论文考虑了被阿片类药物超极化的神经元。 2 刺穿神经元附近的电刺激诱发的突触后电位具有快速（半最大幅度持续时间 37 +/- 2 ms，n = 65）和在某些情况下缓慢（半最大幅度持续时间 817 +/- 187 ms，n = 3）分量。诱发电位的幅度取决于刺激电压、膜电位，并且在灌注含有河豚毒素（100 nM 至 1 muM，n = 5）或 Co2+（4 mM，n = 2）的溶液期间被消除。3 快速突触后电位主要由谷氨酸和 GABA(A) 受体的激活介导。 GABA(A) 受体拮抗剂荷包牡丹碱 (bicucuilline) (30 μM) 可抑制突触后电位 44 +/- 8% (n = 14)。非 NMDA 受体拮抗剂 6-cyano-7-硝基喹喔啉-2,3-二酮 (10 mu M) 可抑制突触后电位 48 +/- 6% (n = 16)。荷包牡丹碱 (30 μM) 和 6-氰基-7-硝基喹喔啉-2,3-二酮 (10 μM) 联合灌注可抑制突触后电位 93 +/- 1% (n = 8)。额外灌注 NMDA 受体拮抗剂 (+/-)-2-氨基-5-磷酸戊酸 (50 μM) 可抑制 94 +/- 1% (n = 3) 的突触电位。4 在 12% (8/65) 的神经元中观察到缓慢的抑制性突触后电位。它们在 -100 和 -110 mV 之间反转极性，并通过灌输螺哌隆 (1 mu M，n = 2) 而被消除，但 α(2) 拮抗剂咪唑克生 (3 mu M，n = 2) 则不会。5 选择性 mu 受体激动剂抑制所有测试的神经元中的快速突触后电位，这些神经元未直接被阿片类药物超极化。 Met-脑啡肽（30μM）和Tyr-D-Ala-Gly-MePhe-Glyol（3μM）分别抑制突触后电位53+/-3%和49+/-3%。这种作用被纳洛酮（1μM，n=3）完全拮抗。选择性 δ 受体激动剂 Tyr-D-Pen-Gly-Phe-D-Pen-脑啡肽 (3 μM，26 +/- 4%，n = 14) 产生的小量抑制被纳洛酮 (1 μM) 拮抗，但不被选择性 δ 受体拮抗剂纳曲吲哚 (10 nM) 拮抗，表明该作用非特异性 mu 受体激活激动剂。选择性 Kappa 受体激动剂 U50488H (3 μM) 也始终如一地抑制突触后电位 45 +/- 15% (n = 4)。然而，纳洛酮 (1 μM) 并未完全逆转这种效应，表明其具有非特异性作用。6 快速突触后电位的谷氨酸能和 GABA 能成分均被甲硫氨酸脑啡肽（30 μM 中的 10 个）抑制。在 6-氰基-7-硝基喹喔啉-2,3-二酮（10 μM，主要是 GABA 能成分）存在下，甲硫氨酸脑啡肽可抑制突触后电位 55 +/- 5% (n = 12)。甲硫氨酸脑啡肽不影响对通过压力喷射直接施加的 GABA 的反应，表明阿片类药物专门抑制 GABA 的突触前释放。在荷包牡丹碱（30 μM，主要是谷氨酸能成分）存在下，甲硫氨酸脑啡肽（10-30 μM）可抑制突触后电位 48 +/- 6%（n = 11）。在荷包牡丹碱和 6-氰基-7-硝基喹喔啉-2,3-二酮同时存在的情况下，甲硫氨酸脑啡肽将突触电位的小残留成分抑制了 42 +/- 15% (n = 2)。7 在 11% (10/94) 的未被阿片类药物直接超极化的神经元中也观察到频繁的自发突触电位。这些被荷包牡丹碱（30 μM，n = 5）可逆地消除，并被甲硫氨酸脑啡肽（30 μM，n = 6）显着抑制，但不受 6-氰基-7-硝基喹喔啉-2,3-二酮（10 μM，n = 2）的影响。8 总之，在整个过程中，电刺激会诱发快速谷氨酸能和 GABA 能突触电位。外侧和腹外侧导水管周围灰色。在一些神经元中也引起了缓慢的抑制性突触电位。作用于 mu 受体的阿片类药物抑制整个大脑区域突触电位的 GABA 能和谷氨酸能成分。
1 Membrane properties of rat periaqueductal gray neurones were investigated by use of intracellular recordings from single neurones in brain slices. Morphological properties and anatomical location of each impaled neurone were characterized by intracellular staining with biocytin. The present paper considers the properties of electrically-evoked and spontaneous postsynaptic potentials impinging on periaqueductal gray neurones, and the actions of opioids on postsynaptic potentials in neurones which were not directly hyperpolarized by opioids. The preceding paper considers neurones which were hyperpolarized by opioids.2 Electrical stimulation in the vicinity of impaled neurones evoked postsynaptic potentials having fast (duration at half-maximal amplitude 37 +/- 2 ms, n = 65) and in some cases slow (duration at half-maximal amplitude 817 +/- 187 ms, n = 3) components. Amplitudes of evoked potentials were dependent on stimulus voltage, membrane potential, and were abolished during superfusion with solutions containing tetrodoxotoxin (100 nM to 1 mu M, n = 5) or Co2+ (4 mM, n = 2).3 Fast postsynaptic potentials were mediated predominantly by activation of glutamate and GABA(A) receptors. The GABA(A)-receptor antagonist, bicucuilline (30 mu M), inhibited postsynaptic potentials by 44 +/- 8% (n = 14). The non-NMDA-receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (10 mu M), inhibited postsynaptic potentials by 48 +/- 6% (n = 16). Combined superfusion of bicuculline (30 mu M) and 6-cyano-7-nitroquinoxaline-2,3-dione (10 mu M) inhibited postsynaptic potentials by 93 +/- 1% (n = 8). Additional superfusion of the NMDA-receptor antagonist, (+/-)-2-amino-5-phosphonovaleric acid (50 mu M) inhibited synaptic potentials by 94 +/- 1% (n = 3).4 Slow inhibitory postsynaptic potentials were observed in 12% (8/65) of neurones. They reversed polarity between -100 and -110 mV, and were abolished by superfusion with spiperone (1 mu M, n = 2), but not the alpha(2)-antagonist, idazoxan (3 mu M, n = 2).5 Selective mu-receptor agonists inhibited fast postsynaptic potentials in all neurones tested which were not directly hyperpolarized by opioids. Met-enkephalin (30 mu M) and Tyr-D-Ala-Gly-MePhe-Glyol (3 mu M) inhibited postsynaptic potentials by 53 +/- 3% and 49 +/- 3%, respectively. This effect was completely antagonised by naloxone (1 mu M, n = 3). A small inhibition produced by the selective delta-receptor agonist, Tyr-D-Pen-Gly-Phe-D-Pen-enkephalin (3 mu M, 26 +/- 4%, n = 14), was antagonized by naloxone (1 mu M), but not by the selective delta-receptor antagonist, naltrindole (10 nM), suggesting non-specific mu-receptor activation by this agonist. The selective Kappa-receptor agonist, U50488H (3 mu M), also consistently inhibited postsynaptic potentials by 45 +/- 15% (n = 4). However, this effect was not fully reversed by naloxone (1 mu M) suggesting a non-specific action.6 Both glutamatergic and GABAergic components of fast postsynaptic potentials were inhibited by Met-enkephalin (10 of 30 mu M). Met-enkephalin inhibited postsynaptic potentials by 55 +/- 5% (n = 12) in the presence of 6-cyano-7-nitroquinoxaline-2,3-dione (10 mu M, predominantly GABAergic component). Met-enkephalin did not affect the response to GABA applied directly by pressure ejection, indicating that opioids exclusively inhibited presynaptic release of GABA. Met-enkephalin (10-30 mu M) inhibited postsynaptic potentials by 48 +/- 6% (n = 11) in the presence of bicuculline (30 mu M, predominantly glutamatergic component). In the presence of both bicuculline and 6-cyano-7-nitroquinoxaline-2,3-dione, Met-enkephalin inhibited the small residual component of the synaptic potential by 42 +/- 15% (n = 2).7 Frequent spontaneous synaptic potentials were also observed in 11% (10/94) of the neurones which were not directly hyperpolarized by opioids. These were reversibly abolished by bicuculline (30 mu M, n = 5) and substantially inhibited by Met-enkephalin (30 mu M, n = 6), but were unaffected by 6-cyano-7-nitroquinoxaline-2,3-dione (10 mu M, n = 2).8 In conclusion, fast glutamatergic and GABAergic synaptic potentials were evoked by electrical stimulation throughout the lateral and ventrolateral periaqueductal gray. Slow inhibitory synaptic potentials were also evoked in some neurones. Opioids acting on mu-receptors inhibited both GABAergic and glutamatergic components of synaptic potentials throughout this brain region.