Lo Wan-Chen, Chan Julie Y H, Tung Che-Se, Tseng Ching-Jiunn
Department of Medical Education and Research, Kaohsiung Veterans General Hospital, 386 Ta-Chung 1st Road, Kaohsiung 813, Taiwan, ROC.
Eur J Pharmacol. 2002 Nov 1;454(1):39-45. doi: 10.1016/s0014-2999(02)02480-9.
Carbon monoxide (CO) has been identified as an endogenous biological messenger in the brain. Heme oxygenase catalyzes the metabolism of heme to biliverdin and CO. Recent studies have demonstrated that CO is involved in central cardiovascular regulation and modulates the baroreflex in the nucleus tractus solitarii of rats. The purpose of the present study was to investigate the possible interaction of CO and excitatory amino acids in the nucleus tractus solitarii. In anesthetized male Sprague-Dawley rats, unilateral intranucleus tractus solitarii microinjection of hematin, a heme molecule cleaved by heme oxygenase to yield CO, or excitatory amino acids L-glutamate produced depressor and bradycardiac effects. Similar cardiovascular effects were observed with several agonists for ionotropic glutamate receptors such as N-methyl-D-aspartate (NMDA), (+/-)-alpha-amino-3-hydroxyl-5-methylisoxazole-4-propanoic acid (AMPA), kainic acid and for metabotropic glutamate (mGlu) receptors, trans-(+/-)-1-amino-(1S,3R)-cyclopentanedicarboxylic acid (ACPD). Among these agonists, prior administration of the heme oxygenase inhibitor, zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG) (1 nmol), significantly attenuated the cardiovascular effects of hematin, L-glutamate and ACPD. Furthermore, the cardiovascular effects of ACPD were prevented by the selective mGlu receptors antagonist L-2-amino-3-phosphonoprionate (L-AP3). However, pretreatment with ZnDPBG failed to prevent the cardiovascular responses to microinjection of NMDA, AMPA and kainic acid. On the other hand, prior administration of the NMDA receptor antagonist, diazocilpine (MK-801), or (+/-)-2-amino-5-phosphonopentanoic acid (APV) attenuated the depressor and bradycardiac effect of hematin. These results demonstrated that mGlu receptors may couple to the activation of heme oxygenase via the liberation of CO to participate in central cardiovascular regulation. They also suggested that CO and excitatory amino acids may interact in the nucleus tractus solitarii of rats.
一氧化碳（CO）已被确认为大脑中的一种内源性生物信使。血红素加氧酶催化血红素代谢生成胆绿素和CO。最近的研究表明，CO参与中枢心血管调节，并调节大鼠孤束核中的压力感受性反射。本研究的目的是探讨CO与兴奋性氨基酸在孤束核中可能的相互作用。在麻醉的雄性Sprague-Dawley大鼠中，单侧孤束核内微量注射血红素（一种被血红素加氧酶裂解产生CO的血红素分子）或兴奋性氨基酸L-谷氨酸会产生降压和心动过缓效应。用几种离子型谷氨酸受体激动剂如N-甲基-D-天冬氨酸（NMDA）、（±）-α-氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）、 kainic酸以及代谢型谷氨酸（mGlu）受体激动剂反式-（±）-1-氨基-（1S，3R）-环戊烷二羧酸（ACPD）也观察到了类似的心血管效应。在这些激动剂中，预先给予血红素加氧酶抑制剂锌原卟啉2,4-双二醇（ZnDPBG）（1 nmol）可显著减弱血红素、L-谷氨酸和ACPD的心血管效应。此外，选择性mGlu受体拮抗剂L-2-氨基-3-膦丙酸（L-AP3）可阻止ACPD的心血管效应。然而，用ZnDPBG预处理未能阻止对微量注射NMDA、AMPA和kainic酸的心血管反应。另一方面，预先给予NMDA受体拮抗剂地卓西平（MK-801）或（±）-2-氨基-5-膦戊酸（APV）可减弱血红素的降压和心动过缓效应。这些结果表明，mGlu受体可能通过释放CO与血红素加氧酶的激活偶联，参与中枢心血管调节。它们还提示，CO与兴奋性氨基酸可能在大鼠孤束核中相互作用。
