Activation of PAC(1) and VPAC receptor subtypes elicits differential physiological responses from sympathetic preganglionic neurons in the anaesthetized rat.
Activation of PAC(1) and VPAC receptor subtypes elicits differential physiological responses from sympathetic preganglionic neurons in the anaesthetized rat.
复制标题
PAC(1) 和 VPAC 受体亚型的激活会引起麻醉大鼠交感神经节前神经元的不同生理反应。
DOI：
10.1111/j.1476-5381.2012.02045.x
复制
发表时间：
2012
影响因子：
7.3
通讯作者：
Farnham,MelissaMJ
中科院分区：
文献类型：
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作者：
Inglott,MelissaA;Lerner,EthanA;Pilowsky,PaulM;Farnham,MelissaMJ
背景和目的垂体腺苷酸环化酶激活肽（PACAP）是一种具有中枢和外周心血管作用的兴奋性神经肽。鞘内注射PACAP会增加内脏交感神经活动和心率，但不会增加平均动脉压（MAP）。我们假设三种PACAP受体（PAC 1、VPAC 1和VPAC 2）在中枢心血管控制中具有不同的作用，并且它们的总和效应导致在鞘内PACAP注射后观察到的MAP反应的缺乏。实验方法使用选择性激动剂和拮抗剂施用到乌拉坦麻醉的、切断迷走神经和人工通气的雄性Sprague-道利大鼠。当被Maxadilan激活时，PAC 1受体增加MAP。当两者都被血管活性肠肽激活或仅VPAC 1受体被激活时，VPAC受体降低MAP。PAC 1和VPAC 2受体拮抗剂PACAP（6-38）没有心血管效应，表明PACAP不是紧张性释放的.CONCLUSIONS AND IMPLICATIONSPACAP神经传递不负责中枢心血管控制机制的瞬间紧张性调节。然而，脊髓内的PACAP释放可能对交感神经流出具有多效性作用，这取决于突触后受体类型。在麻醉的Sprague-道利大鼠中，当鞘内注射PACAP-38激活时，PAC 1和VPAC受体亚型产生相反的血压变化，导致MAP无净变化。
BACKGROUND AND PURPOSEPituitary adenylate cyclase‐activating polypeptide (PACAP) is an excitatory neuropeptide with central and peripheral cardiovascular actions. Intrathecal PACAP increases splanchnic sympathetic nerve activity and heart rate, but not mean arterial pressure (MAP). We hypothesize that the three PACAP receptors (PAC1, VPAC1and VPAC2) have different actions in central cardiovascular control, and that their summed effect results in the lack of MAP response observed following intrathecal PACAP injection.EXPERIMENTAL APPROACHThe effects of the PACAP receptors on baseline cardiovascular parameters were investigated using selective agonists and antagonists administered into the intrathecal space of urethane‐anaesthetized, vagotomized and artificially ventilated male Sprague‐Dawley rats.KEY RESULTSSelective activation of the PACAP receptors had different effects on MAP. When activated by maxadilan, PAC1receptors increased MAP. The VPAC receptors decreased MAP when both were activated with vasoactive intestinal polypeptide or when only VPAC1receptors were activated. The PAC1and VPAC2receptor antagonist PACAP(6–38) had no cardiovascular effects, suggesting that PACAP is not tonically released.CONCLUSIONS AND IMPLICATIONSPACAP neurotransmission was not responsible for the moment‐to‐moment tonic regulation of central cardiovascular control mechanisms. Nevertheless, PACAP release within the spinal cord may have pleiotropic effects on sympathetic outflow depending on the postsynaptic receptor type. PAC1and VPAC receptor subtypes produced opposing changes in blood pressure when activated by intrathecal PACAP‐38 in the anaesthetized Sprague‐Dawley rat, resulting in no net change in MAP.