Evidence for the presence of regional differences in the subtype specificity of muscarinic receptors in rabbit lower urinary tract
Evidence for the presence of regional differences in the subtype specificity of muscarinic receptors in rabbit lower urinary tract
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DOI：
10.1016/s0022-5347(01)65257-1
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发表时间：
1997-02-01
影响因子：
6.6
通讯作者：
Weiss, RM
中科院分区：
文献类型：
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作者：
Mutoh, S;Latifpour, J;Weiss, RM
为了阐明毒蕈碱类胆碱能受体介导下尿路收缩反应的亚型特异性，我们研究了家兔膀胱囊、膀胱底和尿道中毒蕈碱类受体的收缩和生化特性。在不存在和存在不同浓度的毒蕈碱亚型选择性拮抗剂的情况下，构建了增加浓度的等长收缩响应曲线。膀胱穹窿、膀胱基底和尿道对碳水化合物引起的收缩反应表现出不同的功效和效力。膀胱穹窿和膀胱基部的E（max）值明显大于尿道，ED、、值明显小于尿道。计算一系列毒蕈碱类拮抗剂的pA(2)值，即拮抗剂亲和常数（K-B）的负对数，即阿托品（非选择性），吡仑西平（M(1)选择性），甲氧曲明（M(1)选择性），和4-DAMP （M1N3选择性）表明，碳水化合物诱导的膀胱穹丘和膀胱基底的收缩反应是通过M(3)受体亚型介导的，而碳水化合物诱导的尿道收缩反应可能是通过M(1)和/或M(3)以及可能的M(2)亚型介导的。毒蕈碱类胆碱能拮抗剂抑制[H-3]喹啉苯基苯磺酸盐与膀胱穹球、膀胱基部和尿道的结合，亲和顺序如下：阿托品> - 4-DAMP >甲氧曲明>哌嗪。结合数据表明，M(2)受体亚型在所有三个区域均占主导地位。
To elucidate the subtype specificity of muscarinic cholinergic receptors in mediating contractile responses in the lower urinary tract, we investigated contractile and biochemical properties of muscarinic receptors in bladder dome, bladder base and urethra of the rabbit. Isometric contractile response curves to increasing concentrations of carbachol were constructed in the absence and presence of various concentrations of subtype selective muscarinic antagonists. Bladder dome, bladder base, and urethra demonstrate different characteristics in terms of efficacy and potency with respect to carbachol-induced contractile responses. E(max) values are significantly larger and ED,, values are significantly smaller in bladder dome and bladder base than in urethra. Calculation of the pA(2) values, the negative logarithm of the antagonist affinity constant (K-B), for a series of muscarinic antagonists, i.e., atropine (nonselective), pirenzepine (M(1) selective), methoctramine (M(1) selective), and 4-DAMP (M1N3 selective) indicate that the carbachol-induced contractile response in bladder dome and bladder base is mediated through the M(3) receptor subtype whereas the carbachol-induced contractile response in urethra is probably mediated through the M(1) and/or M(3) and possibly M(2) subtypes. Muscarinic cholinergic antagonists inhibit [H-3]quinulidinyl benzilate binding to bladder dome, bladder base and urethra with the following rank order of affinities: atropine > 4-DAMP > methoctramine > pirenzepine. The binding data indicate the predominance of the M(2) receptor subtype in all three regions.