刺激大鼠孤束核中的5-羟色胺3受体所诱导的压力感受器反射抑制

Baroreceptor reflex inhibition induced by the stimulation of serotonin3 receptors in the nucleus tractus solitarius of the rat.

作者信息

Merahi N, Orer H S, Laporte A M, Gozlan H, Hamon M, Laguzzi R

机构信息

INSERM U288, Neurobiologie Cellulaire et Fonctionnelle, CHU Pitié-Salpêtrière, Paris, France.

出版信息

Neuroscience. 1992;46(1):91-100. doi: 10.1016/0306-4522(92)90011-p.

DOI:10.1016/0306-4522(92)90011-p

PMID:1350667

Abstract

Previous studies suggested that in the nucleus tractus solitarius, cardiovascular responses to serotonin may involve the simultaneous activation of more than one receptor subtype. In the present study, the cardiovascular effects of the local application of serotonin and different serotonin3 agonists and antagonists into the nucleus tractus solitarius were analysed in intact and unilaterally ganglionectomized rats. Unilateral injections of serotonin (5-15 nmol) produced a dose-dependent increase in blood pressure and partially antagonized the arterial baroreflex responses evoked by an i.v. injection of phenylephrine. Similar blood pressures response were obtained after unilateral microinjections of phenylbiguanide (5 nmol) and 2-methyl-serotonin (5 nmol), two serotonin3 receptor agonists. Bilateral microinjections of serotonin or phenylbiguanide produced more pronounced blood pressure effects and antagonized completely the baroreflex responses. Both blood pressure and baroreflex effects were antagonized by prior injections of specific serotonin3 antagonists such as zacopride (100 pmol) and ondansetron (100 pmol). Concomitant autoradiographic studies performed in intact and ganglionectomized rats, using [125I]iodozacopride, confirmed that serotonin3 receptors in the nucleus tractus solitarius are mainly located on vagal afferent fibers. In addition, serotonin microinjections made in the nucleus tractus solitarius ipsilateral to the ganglionectomy revealed a significant reduction in cardiovascular responses compared to intact animals. These results suggest that in the nucleus tractus solitarius of the rat, serotonin is involved in the reflex regulation of blood pressure through the stimulation of serotonin3 receptors presumably located on vagal afferent fibers. Since bicuculline antagonized the serotonin-mediated pressor responses, a serotonin3-dependent activation of an inhibitory GABAergic system within the nucleus tractus solitarius might be involved in blood pressure regulatory mechanisms.

摘要

先前的研究表明，在孤束核中，5-羟色胺对心血管系统的反应可能涉及不止一种受体亚型的同时激活。在本研究中，分析了在完整和单侧神经节切除的大鼠中，向孤束核局部应用5-羟色胺以及不同的5-羟色胺3激动剂和拮抗剂对心血管系统的影响。单侧注射5-羟色胺（5-15 nmol）可使血压呈剂量依赖性升高，并部分拮抗静脉注射去氧肾上腺素所诱发的动脉压力反射反应。单侧微量注射5-羟色胺3受体激动剂苯乙双胍（5 nmol）和2-甲基-5-羟色胺（5 nmol）后，也获得了类似的血压反应。双侧微量注射5-羟色胺或苯乙双胍可产生更明显的血压效应，并完全拮抗压力反射反应。预先注射特异性5-羟色胺3拮抗剂如扎考必利（100 pmol）和昂丹司琼（100 pmol），可拮抗血压和压力反射效应。使用[125I]碘扎考必利对完整和神经节切除大鼠进行的同步放射自显影研究证实，孤束核中的5-羟色胺3受体主要位于迷走传入纤维上。此外，与完整动物相比，在神经节切除侧的孤束核中微量注射5-羟色胺后，心血管反应显著降低。这些结果表明，在大鼠孤束核中，5-羟色胺可能通过刺激可能位于迷走传入纤维上的5-羟色胺3受体，参与血压的反射调节。由于荷包牡丹碱可拮抗5-羟色胺介导的升压反应，孤束核内5-羟色胺3依赖性激活抑制性γ-氨基丁酸能系统可能参与血压调节机制。