Characterization of the tachykinin NK<sub>2</sub> receptor in the human bronchus: influence of amastatin‐sensitive metabolic pathways

Astolfi, M.; Treggiari, Stefano; Giachetti, Antonio; Meini, Stefania; Maggi, Carlo Alberto; Manzini, Stefano

doi:10.1111/j.1476-5381.1994.tb14775.x

Cited by 12 publications

(6 citation statements)

References 23 publications

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“…An important finding of the present study is that the NK 2 receptor is the predominant if not the exclusive mediator of the excitatory effect of tachykinins in the smooth muscle of the human ureter. This is in keeping with the results of previous studies, performed on smooth muscles from the human urinary bladder (Maggi et al , 1988b; Dion et al , 1990), gastrointestinal (ileum, colon and oesophagus) (Maggi et al , 1989; Giuliani et al , 1991; Huber et al , 1993) and respiratory tract (Naline et al , 1989; Astolfi et al , 1994; Dion et al , 1990), although excitatory responses mediated by tachykinin NK 1 receptors have also been described in selected cases as the circular muscle of the human ileium (Zagorodnyuk et al , 1997) and small bronchi (Naline et al , 1996).…”

Section: Discussionsupporting

confidence: 90%

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

Patacchini

Santicioli

Zagorodnyuk

et al. 1998

British J Pharmacology

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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.

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Section: Discussionsupporting

confidence: 90%

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

Patacchini

Santicioli

Zagorodnyuk

et al. 1998

British J Pharmacology

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“…Tachykinin family members are prone to different levels of biodegradation by various endogenous placental peptidases, including neutral endopeptidase 24.11, angiotensin I-converting enzyme, bestatin-sensitive aminopeptidases, and amastatin-sensitive aminopeptidases (35)(36)(37)(38)(39)(40)(41)(42)(43). There is indirect evidence for specific patterns of tachykinin catabolism governed by the localized expression of these enzymes within human placenta tissue (44 -51).…”

Section: Discussionmentioning

confidence: 99%

Neurokinin B Is a Paracrine Vasodilator in the Human Fetal Placental Circulation

Brownbill

Bell

Woods

et al. 2003

The Journal of Clinical Endocrinology & Metabolism

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Neurokinin (NK) B is a member of the tachykinin family of neurotransmitters, exerting hypotensive or hypertensive effects in the mammalian vasculature through synaptic release from peripheral neurons, according to either NK(1) and NK(2) or NK(3) receptor subtype expression, respectively. There is recent evidence that NKB is expressed by the syncytiotrophoblast of the human placenta, an organ that is not innervated. We hypothesized that NKB is a paracrine modulator of tone in the fetal placental circulation. We tested this hypothesis using the in vitro perfused human placental cotyledon. Our data show that NKB is a dilator of the fetal vasculature, causing a maximal 25.1 +/- 4.5% (mean +/- SEM; n = 5) decrease in fetal-side arterial hydrostatic pressure (5- microM NKB bolus; effective concentration in the circulation, 1.89 nM) after preconstriction with U-46619. RT-PCR demonstrated the presence of mRNA for NK(1) and NK(2) tachykinin receptors in the placenta. Using selective receptor antagonists, we found that NKB-induced vasodilation is through the NK(1) receptor subtype. We found no evidence for the involvement of either nitric oxide or prostacyclin in this response. This study demonstrates a paracrine role for NKB in the regulation of fetal placental vascular tone.

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“…Giuliani et al , (1993) found that the activities of linear peptide derivatives of NKA with an N‐terminal aspartyl residue were reduced by an amastatin‐sensitive peptidase. The estimated potency of [βAla 8 ]NKA(4–10) was significantly increased from a pD 2 value of 6.87 to 7.44 by amastatin (Astolfi et al , 1994).…”

Section: Discussionmentioning

confidence: 97%

Tachykinin receptors in the guinea‐pig isolated oesophagus: a complex system

Kerr

Mitchelson

Coupar

1997

British J Pharmacology

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1 The tachykinin receptors mediating contraction of isolated longitudinal strips of the guinea-pig oesophageal body were characterized with substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) as well as the analogues, [Sar 9 ,Met (O 2 ) 11 ]SP, [Nle 10 ]NKA(4 ± 10) and [MePhe 7 ]NKB, selective for NK 1 , NK 2 and NK 3 , receptors, respectively. Experiments were performed both in the absence and presence of a cocktail of peptidase inhibitors, captopril (1 mM), thiorphan (1 mM) and amastatin (20 mM), in order to determine whether membrane bound proteases are important in the metabolism of tachykinins in this preparation. 2 All agonists produced concentration-dependent contractile eects. The presence of the peptidase inhibitors shifted the concentration-response curves of SP, [Nle 10 ]NKA(4 ± 10) and [MePhe 7 ]NKB signi®cantly leftwards and the concentration-response curve of NKB was shifted signi®cantly rightwards. However, the EC 50 values were signi®cantly dierent only for [Nle 10 ]NKA(4 ± 10) and NKB. ]SP produced a small response in the nanomolar concentration range in about 30% of the preparations tested, it is possible that some NK 1 receptors were also present. 4 Assuming competitive antagonism, the NK 2 -selective antagonist SR 48,968 (30 nM) gave apparent pK B values of 8.13 and 8.65 for [Nle 10 ]NKA(4 ± 10) in the absence and presence of peptidase inhibitors, respectively, supporting the presence of NK 2 receptors. 5 The NK 3 -selective antagonist SR 142,801 (0.1 mM), suppressed responses to low (0.1 ± 10 nM) concentrations of [MePhe 7 ]NKB. These contractile responses to [MePhe 7 ]NKB were also abolished by atropine (0.6 mM) suggesting that this response was mediated via cholinergic nerves. 6 It is concluded that the guinea-pig oesophagus is a complex system which has both NK 2 and NK 3 receptors and possibly some NK 1 receptors as well.

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Characterization of the tachykinin NK₂ receptor in the human bronchus: influence of amastatin‐sensitive metabolic pathways

Cited by 12 publications

References 23 publications

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

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

Neurokinin B Is a Paracrine Vasodilator in the Human Fetal Placental Circulation

Tachykinin receptors in the guinea‐pig isolated oesophagus: a complex system

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Characterization of the tachykinin NK2 receptor in the human bronchus: influence of amastatin‐sensitive metabolic pathways

Cited by 12 publications

References 23 publications

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

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

Neurokinin B Is a Paracrine Vasodilator in the Human Fetal Placental Circulation

Tachykinin receptors in the guinea‐pig isolated oesophagus: a complex system

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Characterization of the tachykinin NK₂ receptor in the human bronchus: influence of amastatin‐sensitive metabolic pathways