Wainford Richard D, Kurtz Kristine, Kapusta Daniel R
Department of Pharmacology, Louisiana State University Health Sciences Center, 1901 Perdido St, New Orleans, LA 70112, USA.
Am J Physiol Regul Integr Comp Physiol. 2008 Aug;295(2):R535-42. doi: 10.1152/ajpregu.00043.2008. Epub 2008 Jun 4.
The role(s) of central Galpha-proteins in the regulation of cardiovascular and renal function is unknown. We examined how inhibition/downregulation of central Galphai/Galphao, Galphaz or Galphaq proteins altered the characteristic cardiovascular (depressor), renal excretory (diuretic), and plasma AVP (inhibitory) responses to intracerebroventricular injection of nociceptin/orphanin FQ (N/OFQ) in rats. Before investigation, rats were pretreated intracerebroventricularly with saline vehicle (5 microl, 48 h, n=6), pertussis toxin (PTX; 48-h, 1 microg, n=6), or Galphaz, Galphaq, or scrambled oligodeoxynucleotide (ODN) (25 microg, 24 h, n=6 per group). On the study day, intracerebroventricular N/OFQ (5.5 nmol) or vehicle (5 microl) was injected into pretreated conscious rats. Mean arterial pressure (MAP) and heart rate (HR) were recorded, and urine was collected for 90 min. In vehicle or scrambled ODN groups, intracerebroventricular N/OFQ decreased MAP and HR and produced water diuresis (sensitive to UFP-101, N/OFQ receptor antagonist). The hypotension and bradycardia, but not diuresis, to N/OFQ were abolished in PTX-pretreated rats. In contrast, intracerebroventricular ODN pretreatment markedly blunted (Galphaz) or augmented (Galphaq) the diuresis to intracerebroventricular N/OFQ. In separate studies, the action of central N/OFQ to decrease plasma AVP levels in naïve water-restricted rats was differentially altered by intracerebroventricular Galphaz ODN (blunted) and Galphaq ODN (augmented) pretreatment. These studies demonstrate central Galphai/Galphao activity mediates intracerebroventricular N/OFQ's cardiovascular depressor function. Alternatively, central Galphaz (inhibitory) and Galphaq (stimulatory) activity differentially modulates AVP release to control the pattern of diuresis to intracerebroventricular N/OFQ. These findings highlight the novel selective central Galpha-subunit protein-mediated control of cardiovascular vs. renal excretory function.
中枢Gα蛋白在调节心血管和肾功能中的作用尚不清楚。我们研究了中枢Gαi/Gαo、Gαz或Gαq蛋白的抑制/下调如何改变大鼠对脑室内注射孤啡肽/孤啡肽FQ（N/OFQ）的特征性心血管（降压）、肾脏排泄（利尿）和血浆抗利尿激素（抑制）反应。在研究前，大鼠脑室内预先注射生理盐水载体（5微升，48小时，n = 6）、百日咳毒素（PTX；48小时，1微克，n = 6）或Gαz、Gαq或乱序寡脱氧核苷酸（ODN）（25微克，24小时，每组n = 6）。在研究当天，将脑室内N/OFQ（5.5纳摩尔）或载体（5微升）注射到预先处理过的清醒大鼠体内。记录平均动脉压（MAP）和心率（HR），并收集90分钟的尿液。在载体或乱序ODN组中，脑室内N/OFQ降低了MAP和HR并产生水利尿（对UFP - 101，N/OFQ受体拮抗剂敏感）。在PTX预处理的大鼠中，N/OFQ引起的低血压和心动过缓被消除，但利尿作用未受影响。相反，脑室内ODN预处理显著减弱（Gαz）或增强（Gαq）了脑室内N/OFQ引起的利尿作用。在单独的研究中，中枢N/OFQ降低初生水限制大鼠血浆抗利尿激素水平的作用在脑室内Gαz ODN（减弱）和Gαq ODN（增强）预处理后有不同改变。这些研究表明中枢Gαi/Gαo活性介导脑室内N/OFQ的心血管降压功能。另外，中枢Gαz（抑制性）和Gαq（刺激性）活性差异调节抗利尿激素释放以控制脑室内N/OFQ的利尿模式。这些发现突出了新型的由中枢Gα亚基蛋白介导的对心血管与肾脏排泄功能的选择性控制。
