Bustamante S, Orensanz L M, Barahona M V, García-Sacristán A, Hernández M
Servicio de Urología, Hospital Universitario de Getafe, Madrid, Spain.
Neurourol Urodyn. 2001;20(3):297-308. doi: 10.1002/nau.1007.
The current study was designed to characterize the functionally active tachykinin receptors involved in tachykinin-elicited contractions in the pig intravesical ureter, and to investigate the possible modulation exerted by the natural tachykinins substance P (SP) and neurokinin A (NKA) on the non-adrenergic non-cholinergic (NANC) excitatory ureteral neurotransmission. In pig intravesical ureteral strips pretreated with phosphoramidon (10(-5) mol/L) to block the endopeptidase activities, isometric force recordings showed that SP, NKA, and the NK2 receptor selective agonist [beta-Ala(8)]-NKA (4-10), all three induced contractions, with the following potency order: NKA > [beta-Ala(8) ]-NKA (4-10) > SP. [Sar(9), Met(O(2))(11)]-SP and senktide, selective agonists of the NK1 and NK3 receptors, respectively, failed to modify the ureteral tone. Urothelium removal and incubation with tetrodotoxin (10(-6) mol/L), phentolamine (10(-7) mol/L), propranolol (3 x 10(-6) mol/L), atropine (10(-7) mol/L) and indomethacin (3 x 10(-6) mol/L), did not alter the contraction induced by a submaximal (10(-7) mol/L) dose of [beta-Ala(8)]-NKA (4-10). MEN 10,376 (10(-8)-10(-7) mol/L), a NK2 receptor antagonist, reduced the contraction to 3 x 10(-8) mol/L NKA. GR 82334 (10(-6) -10(-5) mol/L) and SR 142801 (10(-8)-10(-7) mol/L), selective antagonists of the NK1 and NK3 receptors, respectively, did not modify that contraction. In pig intravesical ureteral strips in NANC conditions, SP and NKA induced a potentiation of the contractions to electrical field stimulation (EFS) and to exogenous ATP. The results suggest that the tachykinins evoke a direct contraction of pig intravesical ureteral strips through NK2 receptors located in the smooth muscle. SP and NKA exert an enhancement of the NANC excitatory neurotransmission of the pig intravesical ureter.
本研究旨在鉴定参与猪膀胱内输尿管速激肽诱发收缩的功能活跃的速激肽受体，并研究天然速激肽物质P（SP）和神经激肽A（NKA）对非肾上腺素能非胆碱能（NANC）兴奋性输尿管神经传递可能产生的调节作用。在用磷酰胺（10⁻⁵mol/L）预处理以阻断内肽酶活性的猪膀胱内输尿管条上，等长力记录显示，SP、NKA和NK2受体选择性激动剂[β-丙氨酸（8）]-NKA（4-10）均可诱导收缩，其效力顺序如下：NKA>[β-丙氨酸（8）]-NKA（4-10）>SP。NK1和NK3受体的选择性激动剂[Sar（9），Met（O₂）（11）]-SP和senktide未能改变输尿管张力。去除尿路上皮并与河豚毒素（10⁻⁶mol/L）、酚妥拉明（10⁻⁷mol/L）、普萘洛尔（3×10⁻⁶mol/L）、阿托品（10⁻⁷mol/L）和吲哚美辛（3×10⁻⁶mol/L）一起孵育，并未改变亚最大剂量（10⁻⁷mol/L）的[β-丙氨酸（8）]-NKA（4-10）所诱导的收缩。NK2受体拮抗剂MEN 10,376（10⁻⁸-10⁻⁷mol/L）可将对3×10⁻⁸mol/L NKA的收缩反应降低。NK1和NK3受体的选择性拮抗剂GR 82334（10⁻⁶-10⁻⁵mol/L）和SR 142801（10⁻⁸-10⁻⁷mol/L）并未改变该收缩反应。在NANC条件下的猪膀胱内输尿管条中，SP和NKA可增强对电场刺激（EFS）和外源性ATP的收缩反应。结果表明，速激肽通过位于平滑肌中的NK2受体引起猪膀胱内输尿管条的直接收缩。SP和NKA可增强猪膀胱内输尿管的NANC兴奋性神经传递。
