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

Travis Jerde, R. Saban, D. E. Bjorling, S. Y. Nakada

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Objective. To determine which of the known tachykinin receptor subtypes is predominant in the swine ureter. Materials and methods. Ureters from adult pigs were harvested, cut into longitudinal strips and placed in 10 mL tissue baths containing Krebs buffer, under 4 g of initial tension. The magnitude and frequency of contractions were recorded. Tissues were incubated with 1 μmol/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-response curves to the tachykinins substance P (SP), neurokinin A (NKA) and neuroliinin 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 (EC50) for each of the peptides. The mean (SD) EC50 values were (μmol/L): NKA, 0.2 (0.02); SP, 3.5 (0.7); and NKB, 4.5 (1.7). In addition, the selective NK-2 antagonist (SR 48,968) significantly reduced contractile responses to all peptides, as indicated by a 10-fold rightward shift of the concentration-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 predominant tachykinin receptor subtype responsible for contraction of ureteric smooth muscle. The use of mediators which act on NK-2 receptors may have clinical applications for the treatment of ureteric disease.

Original languageEnglish (US)
Pages (from-to)312-317
Number of pages6
JournalBJU International
Volume83
Issue number3
DOIs
StatePublished - 1999
Externally publishedYes

Fingerprint

Tachykinin Receptors
Neurokinin A
Ureter
Substance P
Neurokinin-2 Receptors
Tachykinins
Swine
Peptides
Neurokinin-1 Receptors
Captopril
Protease Inhibitors
Baths
Smooth Muscle
Buffers
NK 2
CP 96345

Keywords

  • Neurokinins
  • Receptors
  • Ureter
  • Ureteric disease

ASJC Scopus subject areas

  • Urology

Cite this

NK-2 is the predominant tachykinin receptor subtype in the swine ureter. / Jerde, Travis; Saban, R.; Bjorling, D. E.; Nakada, S. Y.

In: BJU International, Vol. 83, No. 3, 1999, p. 312-317.

Research output: Contribution to journalArticle

Jerde, Travis ; Saban, R. ; Bjorling, D. E. ; Nakada, S. Y. / NK-2 is the predominant tachykinin receptor subtype in the swine ureter. In: BJU International. 1999 ; Vol. 83, No. 3. pp. 312-317.
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abstract = "Objective. To determine which of the known tachykinin receptor subtypes is predominant in the swine ureter. Materials and methods. Ureters from adult pigs were harvested, cut into longitudinal strips and placed in 10 mL tissue baths containing Krebs buffer, under 4 g of initial tension. The magnitude and frequency of contractions were recorded. Tissues were incubated with 1 μmol/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-response curves to the tachykinins substance P (SP), neurokinin A (NKA) and neuroliinin 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 (EC50) for each of the peptides. The mean (SD) EC50 values were (μmol/L): NKA, 0.2 (0.02); SP, 3.5 (0.7); and NKB, 4.5 (1.7). In addition, the selective NK-2 antagonist (SR 48,968) significantly reduced contractile responses to all peptides, as indicated by a 10-fold rightward shift of the concentration-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 predominant tachykinin receptor subtype responsible for contraction of ureteric smooth muscle. The use of mediators which act on NK-2 receptors may have clinical applications for the treatment of ureteric disease.",
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N2 - Objective. To determine which of the known tachykinin receptor subtypes is predominant in the swine ureter. Materials and methods. Ureters from adult pigs were harvested, cut into longitudinal strips and placed in 10 mL tissue baths containing Krebs buffer, under 4 g of initial tension. The magnitude and frequency of contractions were recorded. Tissues were incubated with 1 μmol/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-response curves to the tachykinins substance P (SP), neurokinin A (NKA) and neuroliinin 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 (EC50) for each of the peptides. The mean (SD) EC50 values were (μmol/L): NKA, 0.2 (0.02); SP, 3.5 (0.7); and NKB, 4.5 (1.7). In addition, the selective NK-2 antagonist (SR 48,968) significantly reduced contractile responses to all peptides, as indicated by a 10-fold rightward shift of the concentration-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 predominant tachykinin receptor subtype responsible for contraction of ureteric smooth muscle. The use of mediators which act on NK-2 receptors may have clinical applications for the treatment of ureteric disease.

AB - Objective. To determine which of the known tachykinin receptor subtypes is predominant in the swine ureter. Materials and methods. Ureters from adult pigs were harvested, cut into longitudinal strips and placed in 10 mL tissue baths containing Krebs buffer, under 4 g of initial tension. The magnitude and frequency of contractions were recorded. Tissues were incubated with 1 μmol/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-response curves to the tachykinins substance P (SP), neurokinin A (NKA) and neuroliinin 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 (EC50) for each of the peptides. The mean (SD) EC50 values were (μmol/L): NKA, 0.2 (0.02); SP, 3.5 (0.7); and NKB, 4.5 (1.7). In addition, the selective NK-2 antagonist (SR 48,968) significantly reduced contractile responses to all peptides, as indicated by a 10-fold rightward shift of the concentration-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 predominant tachykinin receptor subtype responsible for contraction of ureteric smooth muscle. The use of mediators which act on NK-2 receptors may have clinical applications for the treatment of ureteric disease.

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