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

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.

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