血管活性肠肽、胃泌酸调节素和甘丙肽对豚鼠肺实质对组胺、乙酰胆碱和白三烯D4反应的影响。

Effects of vasoactive intestinal peptide, helodermin and galanin on responses of guinea-pig lung parenchyma to histamine, acetylcholine and leukotriene D4.

作者信息

Conroy D M, Samhoun M N, Piper P J

机构信息

Department of Pharmacology, Hunterian Institute, Royal College of Surgeons, London.

出版信息

Br J Pharmacol. 1991 Dec;104(4):1012-8. doi: 10.1111/j.1476-5381.1991.tb12542.x.

DOI:10.1111/j.1476-5381.1991.tb12542.x

PMID:1725762

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1908852/

Abstract

The effect of vasoactive intestinal peptide (VIP) was studied on the contractile response of guinea-pig lung parenchymal strips (GPP) induced by bronchoconstrictor agonists, such as leukotriene D4 (LTD4), histamine and acetylcholine (ACh). This effect of VIP was compared with helodermin, a peptide that is structurally related to VIP, and galanin, another neuropeptide that is thought to co-exist with VIP. 2. VIP (10 nM) induced a potent and reversible inhibition of the contractions of GPP induced by LTD4 (1-30 pmol) but did not affect those due to ACh (1-100 nmol) or histamine (1-30 nmol). A ten fold higher concentration of VIP (100 nM) did not further inhibit LTD4-induced responses or reduce those induced by histamine or ACh. 3. Helodermin (10 nM) had a similar inhibitory effect on contractions of GPP induced by LTD4 (3-30 pmol) but did not affect contractions induced by histamine (1-10 nmol). 4. Indomethacin (2.8 microM) and salbutamol (10 nM) significantly reduced responses elicited by LTD4 and histamine but not those due to ACh. A ten fold higher concentration of salbutamol (100 nM) further inhibited the contractions due to LTD4 and histamine and at this concentration responses induced by ACh were inhibited. 5. VIP (10 nM) and helodermin (10 nM) significantly reduced the LTD4-induced release of thromboxane A2 (TXA2), measured as TxB2 by radioimmunoassay, from GPP. The smaller release of TxA2 induced by histamine was not significantly reduced in the presence of VIP. 6. In comparative studies, galanin (10-100 nM) did not affect contractions of GPP induced by either LTD4, histamine or ACh. In contrast to VIP and helodermin, both at 0.1-3 nmol, which induced doserelated relaxations of guinea-pig trachea, galanin was inactive on this preparation in doses of up to 3 nmol.7. In conclusion, our results show that contractions of GPP induced by LTD4 are more sensitive to inhibition by VIP and helodermin than are contractions due to histamine or ACh. This inhibition appears to be associated with the different contribution of released TxA2 to contractions evoked by the agonists. VIP and helodermin inhibit the cyclo-oxygenase-dependent component of the LTD4-induced response, as in the case of indomethacin.

摘要

研究了血管活性肠肽（VIP）对支气管收缩激动剂如白三烯D4（LTD4）、组胺和乙酰胆碱（ACh）诱导的豚鼠肺实质条（GPP）收缩反应的影响。将VIP的这种作用与结构上与VIP相关的肽海洛德明以及另一种被认为与VIP共存的神经肽甘丙肽进行了比较。2. VIP（10 nM）可有效且可逆地抑制LTD4（1 - 30 pmol）诱导的GPP收缩，但不影响ACh（1 - 100 nmol）或组胺（1 - 30 nmol）诱导的收缩。浓度高10倍的VIP（100 nM）不会进一步抑制LTD4诱导的反应，也不会降低组胺或ACh诱导的反应。3. 海洛德明（10 nM）对LTD4（3 - 30 pmol）诱导的GPP收缩有类似的抑制作用，但不影响组胺（1 - 10 nmol）诱导的收缩。4. 吲哚美辛（2.8 microM）和沙丁胺醇（10 nM）可显著降低LTD4和组胺引起的反应，但不影响ACh引起的反应。浓度高10倍的沙丁胺醇（100 nM）进一步抑制LTD4和组胺引起的收缩，在此浓度下ACh诱导的反应也受到抑制。5. VIP（10 nM）和海洛德明（10 nM）可显著降低LTD4诱导的GPP中血栓素A2（TXA2）的释放，通过放射免疫测定法以TXB2来衡量。在存在VIP的情况下，组胺诱导的较小的TXA2释放没有显著降低。6. 在比较研究中，甘丙肽（10 - 100 nM）不影响LTD4、组胺或ACh诱导的GPP收缩。与0.1 - 3 nmol时诱导豚鼠气管剂量相关舒张的VIP和海洛德明不同，高达3 nmol剂量的甘丙肽对该制剂无活性。7. 总之，我们的结果表明，LTD4诱导的GPP收缩比组胺或ACh诱导的收缩对VIP和海洛德明的抑制更敏感。这种抑制似乎与释放的TXA2对激动剂诱发收缩的不同贡献有关。VIP和海洛德明抑制LTD4诱导反应中依赖环氧化酶的成分，与吲哚美辛的情况相同。