Vague nerve modulates secretin binding sites in the rat forestomach

Vague nerve modulates secretin binding sites in the rat forestomach
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DOI:
10.1152/ajpgi.1999.276.4.g1052
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发表时间:
1999-04-01
影响因子:
4.5
通讯作者:
Chey, WY
Chey, WY
中科院分区:
医学2区
文献类型:
--
作者:
Kwon, HY;Chang, TM;Chey, WY

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促胰液素对胃运动的抑制作用是众所周知的。据报道,生理剂量的促胰液素通过迷走神经传入通路介导抑制胃运动。促胰液素也引起放松卡巴胆碱刺激的大鼠前胃肌条结合其受体,这表明对外周组织的直接作用。我们推测迷走神经输入可能通过调节前胃分泌素受体的水平而影响分泌素的作用。几种治疗方法,包括迷走神经结扎,迷走神经切断术,辣椒素或秋水仙碱的迷走神经周围的应用,静脉输注河豚毒素,和腹腔注射阿托品,进行了调查分泌素受体结合前胃膜的影响。迷走神经结扎、迷走神经切断术(50%)或迷走神经周围秋水仙碱治疗(40%)可显著降低(45%)(125)I标记的促胰液素与前胃膜的特异性结合。相反,特异性结合的(125)I-分泌素不受周围迷走辣椒素治疗,静脉注射河豚毒素,或腹腔注射阿托品。通过Scatchard分析结合数据,发现迷走神经结扎后前胃膜中高亲和力结合位点的能力显著降低,与假手术组的膜相比。然而,高亲和力结合位点的亲和力、低亲和力结合位点的结合参数和结合特异性没有改变。迷走神经结扎,但不是迷走神经周围辣椒素治疗降低促胰液素对氨甲酰胆碱刺激的收缩离体前胃肌条的抑制作用,导致剂量-反应曲线右移。这些结果表明,迷走神经输入通过轴突运输,分泌素的作用,通过调节分泌素结合位点的能力(但不是亲和力或特异性),至少在大鼠,前胃。
Secretin is well known for its inhibitory action on gastric motility. It has been reported that secretin in a physiological dose inhibits gastric motility through mediation by the vagal afferent pathway. Secretin also elicited relaxation of carbachol-stimulated rat forestomach muscle strips by binding to its receptors, suggesting a direct action on this peripheral tissue. We hypothesized that vagal input may affect the action of secretin by modulating the level of secretin receptor in the forestomach. Several treatments, including vagal ligation, vagotomy, perivagal application of capsaicin or colchicine, intravenous infusion of tetrodotoxin, and intraperitoneal injection of atropine, were performed to investigate their effects on secretin receptor binding to forestomach membranes. Specific binding of (125)I-labeled secretin to forestomach membranes was significantly decreased (45%) by vagal ligation, vagotomy (50%), or perivagal colchicine treatment (40%). On the contrary, specific binding of (125)I-secretin was not affected by perivagal capsaicin treatment, intravenous infusion of tetrodotoxin, or intraperitoneal injection of atropine. By Scatchard analysis of the binding data, the capacity of the high-affinity binding sites in forestomach membranes was found to decrease significantly after vagal ligation compared with membranes from the sham-operated group. However, the affinity at the high-affinity binding sites, the binding parameters of the low-affinity binding sites, and binding specificity were not changed. Vagal ligation but not perivagal capsaicin treatment reduced the inhibitory effect of secretin on bethanechol-stimulated contraction of isolated forestomach muscle strips, causing a right shift in the dose-response curve. These results suggest that vagal input through axonal transport; plays a significant role on secretin action by modulating the capacity of secretin binding sites (but not affinity or specificity), at least in rat, forestomach.