β-肾上腺素能受体与5-羟色胺受体信号在调节大脑皮质神经末梢谷氨酸释放中的突触前相互作用。

Presynaptic cross-talk of beta-adrenoreceptor and 5-hydroxytryptamine receptor signalling in the modulation of glutamate release from cerebrocortical nerve terminals.

作者信息

Wang Su-Jane, Coutinho Victoria, Sihra Talvinder S

机构信息

Department of Pharmacology, University College London, Gower Street, London, WC1E 6BT, U.K.

出版信息

Br J Pharmacol. 2002 Dec;137(8):1371-9. doi: 10.1038/sj.bjp.0705045.

DOI:10.1038/sj.bjp.0705045

PMID:12466248

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1573621/

Abstract

The presynaptic interactions between facilitatory beta-adrenoreceptors and inhibitory 5-hydroxytryptamine (5-HT) receptors modulating glutamate release from cerebrocortical nerve terminals were examined. 2. 4-aminopyridine (4-AP, 1 mM)-evoked glutamate release was facilitated by the membrane permeant cyclic-3',5'-adenosine monophosphate (cAMP) analogue, 8-bromo-cAMP (8-Br-cAMP), used to directly activate cAMP-dependent protein kinase (PKA). 3. The beta-adrenoreceptor agonist, isoprenaline (ISO), effected a concentration-dependent potentiation of 4-AP-evoked glutamate release which was abolished by the beta-adrenoreceptor antagonist, propranolol, and the PKA inhibitor, Rp-cyclic-3',5'-adenosine-monophosphothioate (Rp-cAMPS). 4. 5-HT receptor activation by 100 microM 5-HT produced an inhibition of 4-AP-evoked glutamate release in nerve terminals. The inhibitory effect of 5-HT could be mimicked by the selective 5-HT(1A) receptor agonist, 8-hydroxy-dipropylaminotetralin (8-OH-DPAT) and antagonized by 1-(2-methoxyphenyl)-4-(4-phthalimidobutyl)piperazine (NAN-190). 5. When 5-HT (or 8-OH-DPAT) was used in conjunction with ISO or 8-Br-cAMP, the beta-adrenoreceptor- and PKA-mediated potentiation of glutamate release was abrogated. 6. The inhibitory crosstalk of 5-HT(1A) receptors to beta-adrenoceptor-mediated facilitation of glutamate release was abolished in the presence of NAN-190. 7. Examination of voltage-dependent Ca(2+) influx revealed that, while ISO and 5-HT alone caused a respective potentiation and diminution of the 4-AP-evoked increase in Ca(2+), the co-presence of 5-HT abolished the ISO mediated potentiation of Ca(2+) influx. 8. Together, these results suggest that beta-adrenoreceptors and 5-HT(1A) receptors coexist on the cerebrocortical nerve terminals and that the cross-talk between the two receptor signalling pathways occurs at a locus downstream from cAMP production, possibly at the level of voltage-dependent Ca(2+) influx.

摘要

研究了促进性β-肾上腺素能受体与抑制性5-羟色胺（5-HT）受体之间的突触前相互作用，这些受体调节从大脑皮质神经末梢释放谷氨酸。2. 膜通透性环3',5'-腺苷单磷酸（cAMP）类似物8-溴-cAMP（8-Br-cAMP）用于直接激活cAMP依赖性蛋白激酶（PKA），它促进了4-氨基吡啶（4-AP，1 mM）诱发的谷氨酸释放。3. β-肾上腺素能受体激动剂异丙肾上腺素（ISO）对4-AP诱发的谷氨酸释放产生浓度依赖性增强作用，该作用被β-肾上腺素能受体拮抗剂普萘洛尔和PKA抑制剂Rp-环3',5'-腺苷单磷酸硫代酸盐（Rp-cAMPS）消除。4. 100 microM 5-HT激活5-HT受体可抑制神经末梢中4-AP诱发的谷氨酸释放。5-HT的抑制作用可被选择性5-HT(1A)受体激动剂8-羟基二丙基氨基四氢萘（8-OH-DPAT）模拟，并被1-(2-甲氧基苯基)-4-(4-邻苯二甲酰亚胺丁基)哌嗪（NAN-190）拮抗。5. 当5-HT（或8-OH-DPAT）与ISO或8-Br-cAMP联合使用时，β-肾上腺素能受体和PKA介导的谷氨酸释放增强作用被消除。6. 在存在NAN-190的情况下，5-HT(1A)受体对β-肾上腺素能受体介导的谷氨酸释放促进作用的抑制性串扰被消除。7. 对电压依赖性Ca(2+)内流的检测显示，虽然单独使用ISO和5-HT分别导致4-AP诱发的[Ca(2+)]c增加的增强和减弱，但5-HT的共同存在消除了ISO介导的Ca(2+)内流增强作用。8. 总之，这些结果表明β-肾上腺素能受体和5-HT(1A)受体共存于大脑皮质神经末梢，并且这两种受体信号通路之间的串扰发生在cAMP产生的下游位点，可能在电压依赖性Ca(2+)内流水平。