NK-2 is the predominant tachykinin receptor subtype in the swine ureter

Objective To determine which of the known tachykinin receptor subtypes is p redominant in the swine ureter. Materials and methods Ureters from adult pigs were harvested, cut into long itudinal strips and placed in 10 mt tissue baths containing Krebs buffer, u nder 4 g of initial tension. The magnitude and frequency of contractions we re recorded. Tissues were incubated with 1 mu mol/L solutions of peptidase inhibitors (phosphoramidon and captopril) for 1 h to inhibit degradation of peptides and treated with either CP 96,345 (NK-1 receptor antagonist). SR 48.968 (NK-2 receptor antagonist) or saline (control). Concentration-respon se curves to the tachykinins substance P (SP), neurokinin A (NKA) and neuro kinin B (NKB) were determined. Results Ureteric segments showed a concentration-dependent response to all tachykinins: NKA stimulated increased contractions at a Lower concentration than either SP or NKB (P < 0.05). This was reflected by the difference in the effective concentration required to obtain half the maximal response (E C50) for each of the peptides. The mean (SD EC50 values were (mu mol/L): NK A, 0.2 (0.02): SP. 3.5 (0,7): and NKB, 4.5 (1,7). In addition, the selectiv e NK-2 antagonist (SR 48,968) significantly reduced contractile responses t o all peptides, as indicated by a 10-fold rightward shift of the concentrat ion-response curves (P < 0.05), whereas the,NK-1 antagonist (CP 96.345) had no significant effect, Conclusion These results indicate that NK-2 is the pre-dominant tachykinin receptor subtype responsible for contraction of ureteric smooth muscle. The use of mediators which act on NK-2 receptors may have clinical application s for the treatment of ureteric disease.