Saleh T M, Cechetto D F
Robarts Research Institute, University of Western Ontario, London, Canada.
Am J Physiol. 1995 Mar;268(3 Pt 2):R786-95. doi: 10.1152/ajpregu.1995.268.3.R786.
Previously we demonstrated that glutamatergic and noradrenergic receptors mediate the relay of visceral information through the parabrachial nucleus (PBN) and that calcitonin gene-related peptide (CGRP), substance P (SP), somatostatin (SOM), neurotensin (NT), and cholecystokinin (CCK) may modulate these responses. The interactions of these neurotransmitters and neuropeptides were examined in male Wistar rats (17) that were anesthetized with chloral hydrate and ventilated and in which blood pressure and heart rate were continuously monitored. The left cervical vagus nerve was stimulated at submaximal current intensities to elicit changes in single and multiunit activity of visceral thalamic neurons (VTNs). Peristimulus-time and continuous-time histograms of VTN activity were made before and after 200-nl injections of peptides, neurotransmitter agonists or antagonists, or artificial cerebrospinal fluid into the PBN. Combined injection of CGRP and SP into the PBN produced a synergistic inhibition of spontaneous VTN activity and the vagally evoked VTN response. Combined injection of NT and phenylephrine (PE) into the PBN produced only an additive increase in the spontaneous activity of VTNs. Prior administration of SOM in the PBN blocked the excitatory action of an alpha-adrenergic agonist (phenylephrine) injection on the spontaneous activity of VTNs, whereas CGRP, SP, or CCK had no effect on the alpha-agonist-induced response. Prior injection of an alpha-adrenergic antagonist (phentolamine) prevented the excitatory effect of NT in the PBN. Injection of CGRP, SP, NT, or CCK into the PBN did not change the response of VTNs to application of glutamate. These results suggest mechanisms for peptide interaction with primary neurotransmitters in the PBN and indicate whether the neuropeptides are acting before the primary neurotransmitter synapse or postsynaptically.
先前我们证明，谷氨酸能和去甲肾上腺素能受体介导内脏信息通过臂旁核（PBN）的传递，并且降钙素基因相关肽（CGRP）、P物质（SP）、生长抑素（SOM）、神经降压素（NT）和胆囊收缩素（CCK）可能调节这些反应。在用水合氯醛麻醉、通气且持续监测血压和心率的雄性Wistar大鼠（17只）中，研究了这些神经递质和神经肽之间的相互作用。以亚最大电流强度刺激左侧颈迷走神经，以引发内脏丘脑神经元（VTN）单单位和多单位活动的变化。在向PBN注射200 nl肽、神经递质激动剂或拮抗剂或人工脑脊液之前和之后，制作了VTN活动的刺激时间直方图和连续时间直方图。将CGRP和SP联合注射到PBN中，对VTN的自发活动和迷走神经诱发的VTN反应产生协同抑制作用。将NT和去氧肾上腺素（PE）联合注射到PBN中，仅使VTN的自发活动产生相加性增加。事先在PBN中给予SOM可阻断α-肾上腺素能激动剂（去氧肾上腺素）注射对VTN自发活动的兴奋作用，而CGRP、SP或CCK对α-激动剂诱导的反应无影响。事先注射α-肾上腺素能拮抗剂（酚妥拉明）可预防NT在PBN中的兴奋作用。向PBN注射CGRP、SP、NT或CCK不会改变VTN对谷氨酸应用的反应。这些结果提示了PBN中肽与初级神经递质相互作用的机制，并表明神经肽是在初级神经递质突触前还是突触后起作用。
