Nicotine and Neurokinin Signaling
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Neurokinin A
Opiate
Our purpose was to characterize the tachykinin receptor type involved in nasal obstruction to exogenous substance P in rhinitic patients. We also attempted to assess biochemical and cellular events associated with this response. Nasal challenges were performed in seven patients with allergic rhinitis. They received increasing doses (10 to 80 nmol) of substance P, of neurokinin A, of the N-terminal fragment of substance P, substance P(1-9), and of saline on 4 different days separated by 14 days. Nasal airway resistance (NAR) increased in a dose-dependent manner on substance P. Maximal increase reached 4.5-fold basal NAR. Response to neurokinin A was significantly lower (< 2-fold basal NAR). No effect was observed on substance P(1-9) and saline. This order of activity [substance P >>neurokinin A > substance P(1-9) = saline] indicates an NK1 receptor-mediated mechanism inducing local vasodilation. No histamine release was found after any of the four challenges. Proteins significantly increased in nasal lavage fluid on both substance P and neurokinin A, whereas substance P(1-9) and saline had no effect. The percentage of albumin increased in nasal lavage fluid from 30 to 50% of total proteins on substance P and neurokinin A, indicating microvascular leakage. Polymorphonuclear cells significantly increased from 9 to 36% on substance P, from 13 to 49% on neurokinin A, and from 13 to 55% on substance P(1-9). Eosinophils increased in five patients on substance P (from 0.1 to 5% for the group), in three patients after neurokinin A, and in two after substance P(1-9). We conclude that, in allergic rhinitis, tachykinins induce nasal obstruction, recruitment of inflammatory cells, and microvascular leakage through a mechanism independent of activation of mast cells. Nasal obstruction is mediated through NK1 receptor activation, whereas albumin leakage and recruitment of inflammatory cells likely involve NK1 and NK2 receptors and a N-terminal peptide activation site.
Neurokinin A
Tachykinin receptor 1
Neurogenic inflammation
Neurokinin B
Tachykinin receptor
NK1 receptor antagonist
Basal (medicine)
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Neurokinins are a family of peptides which are released from sensory nerves. This family involves substance P, neurokinin A and B which stimulate neurokinin-NK1, -NK2 and -NK3 receptors respectively. The neurokinins as well as C.G.R.P. (calcitonin gene related peptide) and V.I.P. (vasoactive intestinal peptide) are the mediators of the non adrenergic non cholinergic (N.A.N.C.) nervous system. All these peptides can be released by nerve fibres innervating the skin. They are mainly inflammatory mediators. At skin level, the neurokinin induce itch, wheal and flare. Itch and flare are partly due to histamine release from mast cells in response to substance P.
Neurokinin A
Neurokinin B
Tachykinin receptor
Neurogenic inflammation
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Neurokinin A
Neurokinin B
Tachykinin receptor
Eledoisin
Tachykinin receptor 1
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Neurokinin A
Eledoisin
Neurokinin B
Capsaicin
Tachykinin receptor
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Substance P and neurokinin A (substance K) were infused into the coeliac artery of anaesthetized rats at doses of 0.06-20 nmol min-1. Both tachykinins caused contractions of the stomach, the threshold dose of neurokinin A being 10 times lower than of substance P. The dose-response curve for substance P was flatter than that for neurokinin A. On circular muscle strips from the rat gastric corpus in vitro, the dose-response curves for both tachykinins were parallel, neurokinin A being 10 times more potent than substance P. The contractions in response to 10 microM neurokinin A and to 30 microM substance P were 58 and 54%, respectively, of the maximal contraction to bethanechol (1 mM). The effect of substance P was reduced by atropine both in vivo and in vitro. In vitro, the contractions to substance P were also reduced by tetrodotoxin but left unaffected by methysergide. The action of neurokinin A was not affected by these drugs. It is concluded that neurokinin A contracts rat stomach by a direct action on the circular smooth muscle, whereas the action of substance P is mediated, at least in part, by cholinergic interneurones.
Neurokinin A
Bethanechol
Methysergide
Neurokinin B
Tetrodotoxin
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Neurokinin A
Capsaicin
Neurokinin B
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Substance P and neurokinin A have been shown to be present in the sensory airway innervation. In animals and in humans, both in vitro and in vivo, neurokinin A is a more potent bronchoconstrictor than substance P, suggesting that NK-2 receptors mediate their bronchoconstrictor action. Pharmacological studies on rat airways and in asthmatic patients have shown that a large part of the bronchoconstrictor effect of neurokinins is indirect. In animals (rabbit, rat and guinea-pig) neurokinins stimulate the release of acetylcholine from postganglionic cholinergic nerve fibres. Pharmacological studies performed on rat airways suggest that mast cells are also involved. In bronchoalveolar lavage studies in rats, performed immediately following the peak bronchoconstriction caused by the neurokinins, we were able to show that both substance P and neurokinin A cause histamine release into the airways. The physiological actions of neuropeptides are normally terminated by extracellular metabolism. Inhibitors of neutral metalloendopeptidase enhance the in vitro and in vivo bronchoconstrictor effect of the neurokinins. In our rat model, thiorphan not only enhanced the bronchoconstrictor effect of i.v. administered neurokinins, but also enhanced the airway histamine release caused by these sensory neuropeptides.
Neurokinin A
Thiorphan
Tachykinin receptor
Neurokinin B
Tachykinin receptor 1
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Neurokinin A
Primary (astronomy)
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Citations (219)
Identification of the subtype of neurokinin receptor on the endothelium of the rabbit mesenteric artery was demonstrated by comparing the relative potencies of the naturally occurring tachykinins, substance P, neurokinin A and neurokinin B and the highly selective agonists [Glp 6 ,L‐Pro 9 ]SP 6–11 (L‐Pro), [Glp 6 ,D‐Pro 9 ]SP 6–11 (D‐Pro) and N‐succinyl‐[Asp 6 ,MePhe 8 ]SP 6–11 (senktide). Relaxations of the rabbit mesenteric artery to substance P, neurokinin A and neurokinin B were concentration‐dependent and were abolished by the removal of the endothelium. Substance P was more potent than neurokinin A or neurokinin B and L‐Pro was more potent than D‐Pro or senktide. Substance P, neurokinin A and neurokinin B all significantly reduced the nerve‐mediated contractile response in the presence of the endothelium at a concentration of 0.1 μ m , with a rank order of potency substance P > neurokinin A > neurokinin B. At a concentration of 0.1 μ m , L‐Pro also significantly reduced the nerve‐mediated contractile response, unlike D‐Pro and senktide. It is concluded that the relaxation of the rabbit mesenteric artery produced by substance P is mediated by neurokinin‐1 receptors (NK‐1) located on the endothelium. Furthermore, of the analogues, L‐Pro was particularly potent for these receptors.
Neurokinin A
Neurokinin B
Tachykinin receptor
Tachykinin receptor 1
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We investigated the contents of neurokinin A, neurokinin B and substance P in the rabbit iris sphincter muscle, combining HPLC and radioimmunoassay, as our previous reports indicated that a slow component of neurogenic contractions of this muscle is most probably mediated by such tachykinins. The concentrations of these tachykinins were 44.3±8.7 fmol/mg protein, 35.3±10.2 fmol/mg protein and 186.8±29.8 fmol/mg protein (N=4), respectively. These results demonstrated that neurokinin A, neurokinin B and substance P are all present in the rabbit iris sphincter muscle.
Neurokinin A
IRIS (biosensor)
Rabbit (cipher)
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