Department of Pharmacology, School of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes 3900, Ribeirao Preto, SP, 14049-900, Brazil,
Amino Acids. 2013 Oct;45(4):797-810. doi: 10.1007/s00726-013-1523-z. Epub 2013 Jun 7.
In the present study, we report on the cardiovascular effects caused by the microinjection of L-proline (L-Pro) into the supraoptic nucleus (SON) in unanesthetized rats: the possible involvement of ionotropic glutamate receptors in the SON, as well as the peripheral mechanisms involved in the mediation of its cardiovascular effects. We compared the L-Pro effects with those caused by the injection of L-glutamate (L-Glu) into the SON. Microinjection of increasing doses of L-Pro into the SON caused dose-related cardiovascular responses in unanesthetized rats that were similar to those observed after the injection of L-Glu. Pretreatment of the SON with either a selective non-NMDA (NBQX) or a selective NMDA (LY235959) glutamate receptor antagonist blocked the cardiovascular response to L-Pro. The dose-effect curve for the pretreatment with increasing doses of LY235959 was shifted to the left in relation to the curve for NBQX, showing that LY235959 is more potent than NBQX in inhibiting the cardiovascular response to L-Pro. On the other hand, the cardiovascular response to L-Glu was only significantly reduced by pretreatment with NBQX (2 nmol/100 nL), but not affected by LY235959 (2 nmol/100 nL). The pressor response to L-Pro was not affected by intravenous pretreatment with the ganglion blocker pentolinium, but it was blocked by intravenous pretreatment with the V1-vasopressin receptor antagonist dTyr(CH2)5(Me)AVP. In conclusion, these results suggest that L-Pro has a selective receptor that is sensitive to ionotropic glutamate receptor antagonists. Its activation in the SON results in vasopressin release into the systemic circulation, causing pressor and bradycardiac responses.
在本研究中，我们报告了将 L-脯氨酸（L-Pro）微注射到未麻醉大鼠的视上核（SON）中引起的心血管效应：SON 中离子型谷氨酸受体的可能参与，以及介导其心血管效应的外周机制。我们将 L-Pro 的作用与 L-谷氨酸（L-Glu）注射到 SON 中引起的作用进行了比较。将递增剂量的 L-Pro 微注射到 SON 中会引起未麻醉大鼠的剂量相关心血管反应，这些反应类似于注射 L-Glu 后观察到的反应。用选择性非 NMDA（NBQX）或选择性 NMDA（LY235959）谷氨酸受体拮抗剂预先处理 SON，可阻断 L-Pro 引起的心血管反应。用递增剂量的 LY235959 预处理的剂量-效应曲线相对于 NBQX 的曲线向左移位，表明 LY235959 在抑制 L-Pro 引起的心血管反应方面比 NBQX 更有效。另一方面，只有用 NBQX（2 nmol/100 nL）预处理才能显著减少 L-Glu 引起的心血管反应，但 LY235959（2 nmol/100 nL）不影响其反应。L-Pro 的升压反应不受静脉内预先给予节神经阻滞剂戊烷脒的影响，但被静脉内预先给予 V1-加压素受体拮抗剂 dTyr(CH2)5(Me)AVP 阻断。总之，这些结果表明 L-Pro 具有对离子型谷氨酸受体拮抗剂敏感的选择性受体。其在 SON 中的激活导致加压素释放到体循环中，引起升压和心动过缓反应。
