Excitatory motor and electrical effects produced by tachykinins in the human and guinea-pig isolated ureter and guinea-pig renal pelvis

Riccardo Patacchini, Paolo Santicioli, Vladimir Zagorodnyuk, Massimo Lazzeri, Damiano Turini, Carlo Alberto Maggi

Research output: Contribution to journalArticlepeer-review

Abstract

1. In isolated tissue experiments, neurokinin A (NKA) produced concentration-dependent contraction of human and guinea-pig ureter (pD2 = 6.7 and 7.2, respectively); an effect greatly reduced (> 80% inhibition) by the tachykinin NK2 receptor-selective antagonist MEN 11420 (0.1 μM). The tachykinin NK1 and NK3 receptor agonists septide and senktide, respectively, were ineffective. 2. Electrical field stimulation (EFS) of the guinea-pig isolated renal pelvis produced an inotropic response blocked by MEN 11420 (0.01-1 μM). In the same preparation MEN 11420 (0.1 μM) blocked (apparent pK(B) = 8.2) the potentiation of spontaneous motor activity produced by the NK2 receptor-selective agonist [βAla8]NKA(4-10). 3. In sucrose-gap experiments, EFS evoked action potentials (APs) accompanied by phasic contractions of human and guinea-pig ureter, which were unaffected by tetrodotoxin or MEN 11420 (3 μM), but were blocked by nifedipine (1-10 μM). NKA (1-3 μM) produced a slow membrane depolarization with superimposed APs and a tonic contraction with superimposed phasic contractions. NKA prolonged the duration of EFS-evoked APs and potentiated the accompanying contractions. MEN 11420 completely prevented the responses to NKA in both the human and guinea-pig ureter. 4. Nifedipine (1-10 μM) suppressed the NKA-evoked APs and phasic contractions in both human and guinea-pig ureter, and slightly reduced the membrane depolarization induced by NKA. A tonic-type contraction of the human ureter in response to NKA persisted in the presence of nifedipine. 5. In conclusion, tachykinins produce smooth muscle excitation in both human and guinea-pig ureter by stimulating receptors of the NK2 type only. NK2 receptor activation depolarizes the membrane to trigger the firing of APs from latent pacemakers.

Original languageEnglish
Pages (from-to)987-996
Number of pages10
JournalBritish Journal of Pharmacology
Volume125
Issue number5
DOIs
Publication statusPublished - 1998

Keywords

  • Guinea-pig ureter and renal pelvis
  • Human ureter
  • MEN 11420 (Nepadutant)
  • Tachykinin NK receptor
  • Tachykinin receptor antagonists
  • Tachykinins
  • Urinary tract

ASJC Scopus subject areas

  • Pharmacology

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