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 (pD 2 =6.7 and 7.2, respectively); an e ect greatly reduced (480% inhibition) by the tachykinin NK 2 receptor-selective antagonist MEN 11420 (0.1 mM). The tachykinin NK 1 and NK 3 receptor agonists septide and senktide, respectively, were ine ective. 2 Electrical ®eld stimulation (EFS) of the guinea-pig isolated renal pelvis produced an inotropic response blocked by MEN 11420 (0.01 ± 1 mM). In the same preparation MEN 11420 (0.1 mM) blocked (apparent pK B =8.2) the potentiation of spontaneous motor activity produced by the NK 2 receptorselective agonist [bAla 8 ]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 una ected by tetrodotoxin or MEN 11420 (3 mM), but were blocked by nifedipine (1 ± 10 mM). NKA (1 ± 3 mM) 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 mM) 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 NK 2 type only. NK 2 receptor activation depolarizes the membrane to trigger the ®ring of APs from latent pacemakers.

Interstitial cell of Cajal-like cells in the upper urinary tract

“…Higher frequency (8-15 min -1 ) transient potentials of a simple waveform are frequently (83% of cells) recorded in short 'atypical' SMC (90-230µm in length) in the pelvi-calyceal junction of the guinea pig renal pelvis [13,33,40,46,47]. These transient potentials were recorded less frequently in the proximal renal pelvis (10% of recordings) and never in the ureter [16,33].…”

“…In contrast the ureter in dog, rabbit, guinea pig and rat contracts spontaneously in vitro only in the presence of excitatory agonists [12,13] or if the renal pelvis is left attached [2,[14][15][16]. In both uni-calyceal and multi-calyceal mammals, circumferentially cut strips of muscle wall dissected from the same region contract at the same frequency.…”

Pacemakers in the Upper Urinary Tract

“…Investigators have envisaged that autorhythmicity within the upper urinary tract involves a 'chain of coupled linear oscillators' with the most proximal oscillator firing at the highest frequency, The decreasing presence of 'atypical' SMC with distance from the papillate base has been correlated with the decreasing frequency of contraction. Atypical SMC have higher frequency (8-15 min-1) transient potentials of a simple waveform, those potentials are frequently (83% of cells) recorded in short "atypical" SMC (90-230μm in length) in the pelvi-calyceal junction of the guinea pig renal pelvis (Patacchini R et al 1998;Klemm MF et al 1999;Seki N et al 1990, Tsuchida S et al 1992. These transient potentials were recorded less frequently in the proximal renal pelvis (10% of recordings) and never in the ureter (Lang RJ et al 2001;Gosling JA & Dixon JS 1974).…”

“…The ureter in human and pig displays spontaneous contractions in vitro. In contrast the ureter in dog, rabbit, pig and rat contracts spontaneously in vitro only in the presence of excitatory agonists (Morita T et al 1986;Patacchini R et al 1998) or if the renal pelvis is left attached (Golenhofen K et al 1973;Gosling JA et al 1971;Lang RJ et al 2001). In both uni-calyceal and multi-calyceal mammals, circumferentially cut strips of muscle wall dissected from the same region contract at the same frequency.…”

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

“…NKA is the most potent natural tachykinin in exerting a muscle contraction at the human and guinea-pig ureter [Patacchini et al, 1998]. The density of SPimmunoreactive ®bres increases in pathological conditions, such as in¯ammatory processes, of the urinary tract [Pang et al, 1995].…”