Sensitization of visceral afferents to bradykinin in rat jejunum in vitro
Sensitization of visceral afferents to bradykinin in rat jejunum in vitro
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DOI：
10.1111/j.1469-7793.1999.00517.x
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发表时间：
1999-12-01
影响因子：
5.5
通讯作者：
Grundy, D
中科院分区：
文献类型：
--
作者：
Brunsden, AM;Grundy, D
1. 我们使用一种新颖的体外技术研究了炎症介质对大鼠空肠内脏传入放电和缓激肽（BK）传入反应的影响。2．前列腺素E-2（1μM）增强对BK的反应而不影响基础放电，而组胺（100μM）和腺苷（100μM）激活基础放电并增强BK反应。相反，5-HT（100μM）增加基础放电而不影响对BK.3的反应。组胺诱导的传入放电被10μM的H-1（吡拉明）和H-3（硫哌丁胺）抑制，但不被H-2（雷尼替丁）受体拮抗剂抑制。相反，组胺诱导的BK敏化被雷尼替丁（10μM）抑制。4．腺苷诱导的传入放电被 A(1) 受体拮抗剂 DPCPX (10 μM) 阻断，但不受 A(2A) 受体 ZM241385 (10 μM) 阻断的影响。相反，腺苷对 BK 反应的敏化不受两种拮抗剂的影响。基础放电和 BK 诱导的反应不受 A(3) 受体激动剂 IB-MECA (1 μM) 的影响。虽然不排除 A(2B) 受体的参与，但腺苷可能通过 A(1) 受体激活传入放电，而对 BK 的敏化可能涉及 A(1)、A(2A) 或 A(3) 以外的受体，可能是 A(2B) 受体。5。用萘普生（10μM）抑制环加氧酶可防止组胺后的致敏，但不能防止腺苷。6．通过二丁酰 cAMP 模拟致敏作用。这种情况发生时基础放电没有变化，并且不受萘普生的影响。7。总之，BK 诱导的传入放电会被组胺、腺苷和 PGE(2) 增强，但不会被 5-HT 增强。有证据表明，敏化涉及与传入激活不同的机制。致敏作用可能是通过神经末梢介质直接激活后 cAMP 的增加或通过前列腺素释放等间接途径来介导的。
1. We have investigated the effects of inflammatory mediators on visceral afferent discharge and afferent responses to bradykinin (BK) in rat jejunum using a novel in vitro technique.2. Prostaglandin E-2 (1 mu M) augmented responses to BK without affecting basal firing, while histamine (100 mu M) and adenosine (100 mu M) activated basal discharge and enhanced BK responses. In contrast, 5-HT (100 mu M) increased basal discharge without influencing responses to BK.3. Afferent discharge induced by histamine was inhibited by both H-1 (pyrilamine) and H-3 (thioperamide) but not H-2 (ranitidine) receptor antagonists at 10 mu M. In contrast, sensitization to BK induced by histamine was inhibited by ranitidine (10 mu M).4. Afferent discharge induced by adenosine was blocked by the A(1) receptor antagonist DPCPX (10 mu M) but remained unaffected by A(2A) receptor blockade with ZM241385 (10 mu M). In contrast, sensitization of BK responses by adenosine was unaffected by both antagonists. Basal discharge and BK-induced responses were unaffected by the A(3) receptor agonist IB-MECA (1 mu M). While involvement of A(2B) receptors is not excluded, adenosine may activate afferent discharge through A(1) receptors, while sensitization to BK could involve a receptor other than A(1), A(2A) or A(3), possibly the A(2B) receptor.5. Inhibition of cyclo-oxygenase with naproxen (10 mu M) prevented sensitization after histamine but not adenosine.6. Sensitization was mimicked by dibutyryl cAMP. This occurred without changes in basal firing and was unaffected by naproxen.7. In conclusion, afferent discharge induced by BK is augmented by histamine, adenosine and PGE(2), but not by 5-HT. Evidence suggests that sensitization involves separate mechanisms from afferent activation. Sensitization may be mediated by increases in cAMP following direct activation by mediators at the nerve terminal or through indirect pathways such as the release of prostaglandins.