The Tachykinin Peptide Family

Severini, Cinzia; Improta, Giovanna; Falconieri–Erspamer, Giuliana; Salvadori, Severo; Erspamer, V.

doi:10.1124/pr.54.2.285

Cited by 566 publications

(327 citation statements)

References 338 publications

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“…20 Both NKA and substance P (SP), another similarly structured tachykinin, are known to have effects on gastrointestinal motility, vasodilatation, and flushing, and can be associated with effects on lymphocytes and mast cell degranulation. 21 Both NKA and SP are stored and secreted by classical midgut carcinoid tumours. 22 23 Neuropeptide K is an N terminal extended form of NKA.…”

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confidence: 99%

Circulating markers of prognosis and response to treatment in patients with midgut carcinoid tumours

Turner

Johnston

McCance

et al. 2006

Gut

109

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Background and aims: Midgut carcinoid tumours are uncommon tumours with an unpredictable clinical behaviour and few useful prognostic markers. Somatostatin analogues are widely used in treatment but a survival advantage has not been proven. We analysed features associated with poor prognosis and assessed the clinical implications of the biochemical response to therapy. Methods: Clinical and biochemical data were collected for patients with midgut carcinoid tumours attending a tertiary referral neuroendocrine clinic from 1978 to 2000. Using death as the end point, univariate and multivariate survival analyses were performed to identify prognostic indicators. The significance of altering biomarkers with therapy was also studied by including repeated measurements of the most prognostic biochemical parameter in a time dependent covariate survival analysis. Results: We identified 139 patients with sufficient data for our analyses. Factors associated with a poor outcome on univariate analysis included: plasma neurokinin A (NKA), urinary 5-hydroxyindolacetic acid output, age, and >5 liver metastases. Plasma NKA was the strongest and only independent predictor of outcome on multivariate analysis. Patients in whom NKA continued to rise despite somatostatin analogues had a significantly worse survival than those in whom NKA stabilised or fell (one year survival rate 40% v 87%). Time dependent covariate analysis concluded that survival was better predicted by the most recent plasma NKA value rather than by the initial value. Conclusions: Plasma NKA is an accurate marker of prognosis for midgut carcinoid tumours. This is the first paper to support a survival advantage in patients in whom plasma NKA is altered by somatostatin analogues.

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confidence: 99%

Circulating markers of prognosis and response to treatment in patients with midgut carcinoid tumours

Turner

Johnston

McCance

et al. 2006

Gut

109

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“…2 SP is an 11 amino acid neuropeptide, which is released from both the central and the peripheral terminals of the peptidergic small to medium-sized DRG neurons following noxious stimuli. 3 It binds preferentially to the neurokinin type 1 receptor (NK1r). 4 Release of SP in the spinal cord dorsal horn is associated with enhanced synaptic transmission, whereas its release at the periphery gives rise to neurogenic inflammation.…”

Section: Introductionmentioning

confidence: 99%

Role of neurokinin type 1 receptor in nociception at the periphery and the spinal level in the rat

et al. 2015

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Objectives: Noxious stimuli activate small to medium-sized dorsal root ganglion (DRG) neurons. Intense noxious stimuli result in the release of substance P (SP) from the central terminals of these neurons. It binds to the neurokinin type 1 receptor (NK1r) and sensitises the dorsal horn neurons. SP is also released from the peripheral terminals leading to neurogenic inflammation. However, their individual contribution at spinal and peripheral levels to postincisional nociception has not been delineated as yet. Methods: Sprague-Dawley rats were administered different doses (3-100 μg) of an NK1r antagonist (L760735) by intrathecal (i.t.) route before hind paw incision. On the basis of its antinociceptive effect on guarding behaviour, the 30 μg dose was selected for further study. In different sets of animals, this was administered i.t. (postemptive) and intrawound (i.w.). Finally, in another group, drug (30 μg) was administered through both i.t and i.w. routes. The antinociceptive effect was assessed and compared. Expression of SP was examined in the spinal cord. Intrawound concentration of SP and inflammatory mediators was also evaluated. Results: Postemptive i.t. administration significantly attenuated guarding and allodynia. Guarding was alone decreased after i.w. drug treatment. Combined drug administration further attenuated all nociceptive parameters, more so after postemptive treatment. Expression of SP in the spinal cord decreased post incision but increased in the paw tissue. Inflammatory mediators like the nerve growth factor also increased after incision. Conclusion: In conclusion, SP acting through the NK1r appears to be an important mediator of nociception, more so at the spinal level. These findings could have clinical relevance.

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“…In normal physiology, the EC cells of the gut mucosa also contain tachykinins and probably account for these peptides being present in the circulation. 194 NKA is a decapeptide as is NKB. SP has one more amino acid residue.…”

Section: Ardill Circulating Markers For Netsmentioning

confidence: 99%

Circulating markers for endocrine tumours of the gastroenteropancreatic tract

Ardill

2008

Ann Clin Biochem

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The diffuse endocrine system (DES) includes a wide range of secretory cells that may be the source of tumours. Gastroenteropancreatic endocrine (GEP) tumours arising within the DES secrete a variety of peptides and amines that are found in the circulation and are responsible for the syndromes associated with these tumours. In this review, the most common tumours of the GEP tract are outlined and the circulating products of these tumours identified. Where differential diagnosis is difficult these points are addressed. The peptides most commonly secreted by GEP neuroendocrine tumours are identified and described and their biological activities are discussed. Current methods available for measurement of these peptides are described. Attention is drawn towards molecular specificity where appropriate, as many pancreatic and gut peptides fall within families which show considerable homology, such as the tachykinin family or the glucagon family. Other peptides such as gastrin circulate in multiple molecular forms. This homology and diversity may cause difficulty in the interpretation of peptide measurements in the clinical situation if assays are not specific.

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The Tachykinin Peptide Family

Cited by 566 publications

References 338 publications

Circulating markers of prognosis and response to treatment in patients with midgut carcinoid tumours

Circulating markers of prognosis and response to treatment in patients with midgut carcinoid tumours

Role of neurokinin type 1 receptor in nociception at the periphery and the spinal level in the rat

Circulating markers for endocrine tumours of the gastroenteropancreatic tract

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