大鼠和豚鼠颈上神经节之间神经激肽受体药理学的差异。

Differences in neurokinin receptor pharmacology between rat and guinea-pig superior cervical ganglia.

作者信息

Seabrook G R, Main M, Bowery B, Wood N, Hill R G

机构信息

Department of Pharmacology, Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex.

出版信息

Br J Pharmacol. 1992 Apr;105(4):925-8. doi: 10.1111/j.1476-5381.1992.tb09079.x.

DOI:10.1111/j.1476-5381.1992.tb09079.x

PMID:1380375

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1908729/

Abstract

The depolarizations elicited by seven neurokinin receptor agonists were examined in both rat and guinea-pig superior cervical ganglia by use of grease-gap methodology in the presence of tetrodotoxin (0.1 microM). Responses were normalised with respect to 1 microM eledoisin. 2. The rank order of agonist potency in the rat ganglia was senktide greater than substance P greater than substance P methyl ester = eleidosin = Sar-Met-substance P greater than neurokinin B greater than neurokinin A, whereas in guinea-pig superior cervical ganglion (SCG) the rank order was senktide greater than Sar-Met-substance P greater than neurokinin B = eledoisin = substance P methyl ester. The concentration-effect curves for substance P and neurokinin A in guinea-pig ganglia were biphasic which precluded the determination of meaningful potency values. 3. The maximal depolarization achieved by subtype selective ligands was different between these two species. On rat and guinea-pig SCG, the NK3-selective ligand, senktide, produced a maximal depolarization of 27% and 274% respectively, whereas the NK1-selective ligand, substance P methyl ester, produced depolarizations of 77% and 64% respectively. 4. The depolarizations induced by substance P methyl ester and senktide in either species were unaffected by atropine (1 microM), suggesting a lack of involvement of presynaptic neurokinin receptors in the generation of the response. 5. The potency of substance P methyl ester, senktide, and neurokinin A were unaffected by pretreating ganglia with the peptidase inhibitors bacitracin (40 micrograms ml-1), leupeptin (4 micrograms ml-1), and chymostatin (2 micrograms ml-1). Similarly, these peptidase inhibitors had no effect on the maximal depolarizations achieved by any of these agonists.6. It is evident that rat and guinea-pig superior cervical ganglia possess both NK, and NK3 receptors, but that their net contribution to depolarizations are different between the two species. The depolarizations in guinea-pig SCG are mediated predominantly by an NK3 subtype and in rat SCG by an NK, receptor subtype.

摘要

在存在河豚毒素（0.1微摩尔）的情况下，采用油脂间隙法在大鼠和豚鼠颈上神经节中检测了七种神经激肽受体激动剂引发的去极化。将反应相对于1微摩尔的eledoisin进行标准化。2. 在大鼠神经节中激动剂效力的排序为：senktide＞P物质＞P物质甲酯 = eledoisin = 肌氨酸 - 蛋氨酸 - P物质＞神经激肽B＞神经激肽A，而在豚鼠颈上神经节（SCG）中排序为：senktide＞肌氨酸 - 蛋氨酸 - P物质＞神经激肽B = eledoisin = P物质甲酯。豚鼠神经节中P物质和神经激肽A的浓度 - 效应曲线是双相的，这使得无法确定有意义的效力值。3. 这两个物种之间，亚型选择性配体实现的最大去极化不同。在大鼠和豚鼠的SCG上，NK3选择性配体senktide分别产生27%和274%的最大去极化，而NK1选择性配体P物质甲酯分别产生77%和64%的去极化。4. P物质甲酯和senktide在任一物种中诱导的去极化均不受阿托品（1微摩尔）的影响，表明突触前神经激肽受体未参与反应的产生。5. 用肽酶抑制剂杆菌肽（40微克/毫升）、亮抑酶肽（4微克/毫升）和抑糜酶素（2微克/毫升）预处理神经节后，P物质甲酯、senktide和神经激肽A的效力不受影响。同样，这些肽酶抑制剂对这些激动剂中任何一种所实现的最大去极化均无影响。6. 显然，大鼠和豚鼠颈上神经节都同时拥有NK1和NK3受体，但它们对去极化的净贡献在这两个物种之间有所不同。豚鼠SCG中的去极化主要由NK3亚型介导，而大鼠SCG中则由NK1受体亚型介导。