初级感觉传入神经上烟碱样受体的激活调节小鼠肾盂的自律性。
Nicotinic receptor activation on primary sensory afferents modulates autorhythmicity in the mouse renal pelvis.
作者信息
Nguyen M J, Angkawaijawa S, Hashitani H, Lang R J
机构信息
Department of Physiology, School of Biomedical Sciences, Monash University, Clayton, Vic., Australia.
出版信息
Br J Pharmacol. 2013 Nov;170(6):1221-32. doi: 10.1111/bph.12395.
BACKGROUND AND PURPOSE
The modulation of the spontaneous electrical and Ca(2+) signals underlying pyeloureteric peristalsis upon nicotinic receptor activation located on primary sensory afferents (PSAs) was investigated in the mouse renal pelvis.
EXPERIMENTAL APPROACH
Contractile activity was followed using video microscopy, electrical and Ca(2+) signals in typical and atypical smooth muscle cells (TSMCs and ASMCs) within the renal pelvis were recorded separately using intracellular microelectrodes and Fluo-4 Ca(2+) imaging.
KEY RESULTS
Nicotine and carbachol (CCh; 1-100 μM) transiently reduced the frequency and increased the amplitude of spontaneous phasic contractions in a manner unaffected by muscarininc antagonists, 4-DAMP (1,1-dimethyl-4-diphenylacetoxypiperidinium iodide) and pirenzipine (10 nM) or L-NAME (L-Nω-nitroarginine methyl ester; 200 μM), inhibitor of NO synthesis, but blocked by the nicotinic antagonist, hexamethonium or capsaicin, depletor of PSA neuropeptides. These negative chronotropic and delayed positive inotropic effects of CCh on TSMC contractions, action potentials and Ca(2+) transients were inhibited by glibenclamide (Glib; 1 μM), blocker of ATP-dependent K (KATP) channels. Nicotinic receptor-evoked inhibition of the spontaneous Ca(2+) transients in ASMCs was prevented by capsaicin but not Glib. In contrast, the negative inotropic and chronotropic effects of the non-selective COX inhibitor indomethacin were not prevented by Glib.
CONCLUSIONS AND IMPLICATIONS
The negative chronotropic effect of nicotinic receptor activation results from the release of calcitonin gene-related peptide (CGRP) from PSAs, which suppresses Ca(2+) signalling in ASMCs. PSA-released CGRP also evokes a transient hyperpolarization in TSMCs upon the opening of KATP channels, which reduces contraction propagation but promotes the recruitment of TSMC Ca(2+) channels that underlie the delayed positive inotropic effects of CCh.
背景与目的
研究了位于初级感觉传入神经（PSA）上的烟碱样受体激活后，对小鼠肾盂输尿管蠕动相关的自发性电信号和Ca(2+)信号的调节作用。
实验方法
采用视频显微镜观察收缩活动，分别用细胞内微电极和Fluo-4 Ca(2+)成像记录肾盂内典型和非典型平滑肌细胞（TSMC和ASMC）的电信号和Ca(2+)信号。
关键结果
尼古丁和卡巴胆碱（CCh；1 - 100 μM）可短暂降低自发性相性收缩的频率并增加其幅度，这种作用不受毒蕈碱拮抗剂4-DAMP（1,1-二甲基-4-二苯乙酰氧基哌啶碘化物）、哌仑西平（10 nM）或NO合成抑制剂L-NAME（L-Nω-硝基精氨酸甲酯；200 μM）的影响，但可被烟碱样拮抗剂六甲铵或辣椒素（PSA神经肽耗竭剂）阻断。CCh对TSMC收缩、动作电位和Ca(2+)瞬变的这些负性变时作用和延迟的正性变力作用被格列本脲（Glib；1 μM）抑制，格列本脲是ATP依赖性钾通道（KATP）的阻滞剂。辣椒素可阻止烟碱样受体诱发的ASMC自发性Ca(2+)瞬变的抑制，但格列本脲不能。相反，非选择性COX抑制剂吲哚美辛的负性变力作用和负性变时作用不受格列本脲的影响。
结论与意义
烟碱样受体激活的负性变时作用源于PSA释放降钙素基因相关肽（CGRP），其抑制了ASMC中的Ca(2+)信号传导。PSA释放的CGRP在KATP通道开放时也会引起TSMC的短暂超极化，这减少了收缩传播，但促进了TSMC Ca(2+)通道的募集，这些通道是CCh延迟正性变力作用的基础。
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