NK2 tachykinin receptors mediate contraction of the pig intravesical ureter: Tachykinin-induced enhancement of non-adrenergic non-cholinergic excitatory neurotransmission

The current study was designed to characterize the functionally active tach ykinin receptors involved in tachykinin-elicited contractions in the pig in travesical ureter, and to investigate the possible modulation exerted by th e natural tachykinins substance P (SP)and neurokinin A (NKA) on the non-adr energic non-cholinergic (NANC) excitatory ureteral neurotransmission. In pi g 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, s elective agonists of the NK1 and NK3 receptors, respectively, failed to mod ify 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 indolmethacin (3 x 10(6) mol/L), did not alte r 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 antagoni st, reduced the contraction to 3 x 10(-8) mom NKA. GR 82331(10(-6)-10(-5) m ol/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 i ntravesical ureteral strips in NANC conditions, SP and NKA induced a potent iation of the contractions to electrical field stimulation (EFS) and to exo genous ATP. The results suggest that the tachykinins evoke a direct contrac tion of pig intravesical ureteral strips through NK2 receptors located in t he smooth muscle. SP and NKA exert an enhancement of the NANC excitatory ne urotransmission of the pig intravesical ureter. Neurourol. Urodynam. 20:297 -308, 2001. (C) 2001 Wiley-Liss, Inc.