Substance P and neurokinin A are codistributed and colocalized in the porcine gastrointestinal tract

Schmidt, Peter T.; Poulsen, Steen Seier; Rasmussen, T. N.; Bersani, Maurizio; Holst, Jens J.

doi:10.1016/0196-9781(91)90045-q

Cited by 64 publications

(25 citation statements)

References 17 publications

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“…Each of the peptides binds to each of the three tachykinin receptors, the NK 1 , NK 2 and NK 3 receptors (Maggi 1995), and some of these peptides may be located in the same neurons (Schmidt et al 1991). The tachykinins appear to diffuse for significant distances within tissue, such that they can be collected from the bathing solution around segments of ileum in vitro and from the venous effluent of the intestines in vivo (Holzer and Holzer-Petsche 1997a;Lippi et al 1998).…”

Section: Introductionmentioning

confidence: 98%

Neurons bearing NK 3 tachykinin receptors in the guinea-pig ileum revealed by specific binding of fluorescently labelled agonists

Jenkinson¹,

Morgan²,

Furness³

et al. 1999

Histochemistry and Cell Biology

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The localisation of NK(3) tachykinin receptors in guinea-pig ileum was studied using the fluorescently labelled agonists, Cy3. 5-neurokinin A and Cy3.5-kassinin. Binding to nerve cell bodies in the myenteric and submucosal plexuses was visualised using confocal microscopy. Binding to NK(1) receptors was blocked by the NK(1) receptor antagonist, CP-99994. NK(3) receptors, demonstrated by binding in the presence of CP-99994, occurred in 72% of myenteric and 38% of submucosal neurons. Colocalisation with other markers was examined to deduce the classes of neurons with NK(3) receptors. In myenteric ganglia, NK(3) receptors were present on the following: 73% of calbindin-immunoreactive (IR) intrinsic primary afferent neurons, 63% of calretinin-IR excitatory motor neurons and ascending interneurons, 63% of nitric oxide synthase-IR inhibitory motor neurons and descending interneurons, 79% of strongly neuropeptide Y (NPY)-IR secretomotor neurons, 67% of weakly NPY-IR descending interneurons and motor neurons, and 46% of NK(1) receptor-IR neurons. In submucosal ganglia, NK(3) receptors were on 65% of calretinin-IR secretomotor/vasodilator neurons, 81% of NPY-IR cholinergic secretomotor neurons, 2% of vasoactive intestinal peptide-IR non-cholinergic secretomotor neurons and were completely absent from substance P-IR intrinsic primary afferent neurons. The results support physiological studies suggesting that NK(3) receptors mediate tachykinin transmission between myenteric sensory neurons and to interneurons and/or motor neurons in descending inhibitory and ascending excitatory pathways.

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Section: Introductionmentioning

confidence: 98%

Neurons bearing NK 3 tachykinin receptors in the guinea-pig ileum revealed by specific binding of fluorescently labelled agonists

Jenkinson¹,

Morgan²,

Furness³

et al. 1999

Histochemistry and Cell Biology

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“…TKs acting on NK-1 and NK-2 receptors have been reported to stimulate in vitro pancreatic amylase secretion (12-14, 16, 20, 33), and NK-1 and NK-2 receptors have been detected in the pancreatic acinar cells of guinea pig and mouse (6,11,29,30,32). No information is available on whether acinar cells in the pancreas of these and other animal species express the NK-3 receptor, and little is known on the effects of NK-3 receptor agonists on pancreatic exocrine secretion (7,12,18,20,33).…”

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confidence: 99%

Expression of NK-1 and NK-3 tachykinin receptors in pancreatic acinar cells after acute experimental pancreatitis in rats

Broccardo

Linari²,

Agostini³

et al. 2006

American Journal of Physiology-Gastrointestinal and Liver Physi

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Activation of neurokinin (NK)-1 receptors but not of NK-3 stimulates amylase release from isolated pancreatic acini of the rat. Immunofluorescence studies show that NK-1 receptors are more strongly expressed than NK-3 receptors on pancreatic acinar cells under basal conditions. No studies have examined the expression of the two NK receptor populations in pancreatic acini during pancreatitis in rats. We therefore investigated the relationships between expression of these two tachykinin receptors and experimental acute pancreatitis induced by stimulating pancreatic amylase with caerulein (CK) in rats. Hyperstimulation of the pancreas by CK caused an increase in plasma amylase and pancreatic water content and resulted in morphological evidence of cytoplasmic vacuolization. Immunofluorescence analysis revealed a similar percentage of NK-1 receptor antibody immunoreactive acinar cells in rats with pancreatitis and in normal rat tissue but a larger percentage of NK-3 receptor immunoreactive cells in acute pancreatitis than in normal pancreas. Western blot analysis of NK-1 and NK-3 receptor protein levels after CK-induced pancreatitis showed no change in NK-1 receptors but a stronger increase in NK-3 receptor expression in pancreatic acini compared with normal rats thus confirming the immunofluorescence data. These new findings support previous evidence that substance P-mediated functions within the pancreas go beyond sensory signal transduction contributing to neurogenic inflammation, and they suggest that substance P plays a role in regulating pancreatic exocrine secretion via acinar NK-1 receptors. The significant increase in NK-3 receptors during pancreatic stimulation suggests that NK-3 receptors also intervene in the pathogenesis of mild acute pancreatitis in rats. isolated pancreatic acini; tachykinin receptor distribution; immunofluorescence; Western blot analysis THE NEUROPEPTIDES substance P (SP), neurokinin (NK)-A, and NK-B are primary mammalian tachykinins (TKs) involved in a wide-ranging control of peripheral and central functional activities. Each TK preferentially binds to a specific cell surface receptor subtype belonging to the superfamily of G proteincoupled receptors: SP binds to the NK-1 receptor, NK-A to the NK-2 receptor, and NK-B to the NK-3 receptor. TKs and their receptors are diffusely distributed in the mammalian gastrointestinal tract where they mediate motor, secretory, and circulatory responses (10).To date, few reports exist on the role of the TKs in regulating exocrine pancreatic secretion. TKs acting on NK-1 and NK-2 receptors have been reported to stimulate in vitro pancreatic amylase secretion (12-14, 16, 20, 33), and NK-1 and NK-2 receptors have been detected in the pancreatic acinar cells of guinea pig and mouse (6,11,29,30,32). No information is available on whether acinar cells in the pancreas of these and other animal species express the NK-3 receptor, and little is known on the effects of NK-3 receptor agonists on pancreatic exocrine secretion (7,12,18,20,33). In our recent stud...

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“…As a result, they are often used as models to study a variety of disease mechanisms and different pathophysiological conditions in humans, such as obesity and gastrointestinal dysfunctions (Spurlock and Gabler 2008;Pidsudko et al 2011;Zhang et al 2013). Substance P was reported to be localised in the porcine central nervous system (Barnes et al 1993;Holm et al 1993) and in the nerve fibres innervating many porcine organs (Schmidt et al 1991;Happola et al 1993;Czaja et al 2001;Lamb and Sparrow 2002;Podlasz et al 2003;Pidsudko et al 2008;Podlasz and Wasowicz 2008;Kaleczyc et al 2010). In the pig, substance P can stimulate both endocrine and exocrine pancreatic functions through NK-1 receptors (Schmidt et al 2000).…”

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confidence: 99%

Characterisation, localisation and expression of porcine TACR1, TACR2 and TACR3 genes

Jakimiuk¹,

Podlasz²,

Chmielewska-Krzesińska³

et al. 2017

Vet. Med.

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Substance P is involved in many physiological and pathophysiological processes. This functional diversity is mediated by three neurokinin receptor subtypes (NK1R, NK2R and NK3R) encoded by the TACR1, TACR2 and TACR3 genes, respectively. Despite the increasing interest in using pigs (Sus scrofa) to study human disease mechanisms, the sequences of these receptors are still unconfirmed or in the case of the NK1 receptor, not yet even unpredicted. We employed in silico analysis to define the localisation of the porcine tachykinin receptor genes, and to predict the structures and amino acid sequences of the respective proteins. A reverse transcription polymerase chain reaction (RT-PCR) assay was performed to analyse the expression of tachykinin receptor genes in different porcine tissues. The data show that the TACR1 gene is located on chromosome 3, TACR2 on chromosome 14 and TACR3 on chromosome 8. All three genes encode proteins with structures that incorporate features of G-protein-coupled receptors with sizes of 407, 381 and 464 amino acids, respectively. The receptors display a high degree of similarity to other mammalian neurokinin receptors. The NK1R subtype is expressed in both the central nervous system and peripheral tissues, while NK2R expression seems to be localised mostly to peripheral tissues. The expression of NK3R is found mainly in the central nervous system. This report provides for the first time the results of a comprehensive analysis of the structure and distribution of porcine NK1R, as well as other porcine neurokinin receptors and their genes. We hope that our data may offer an invaluable foundation for the future studies on the function of diverse tachykinin peptides in the central nervous system and peripheral tissues.

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Substance P and neurokinin A are codistributed and colocalized in the porcine gastrointestinal tract

Cited by 64 publications

References 17 publications

Neurons bearing NK 3 tachykinin receptors in the guinea-pig ileum revealed by specific binding of fluorescently labelled agonists

Neurons bearing NK 3 tachykinin receptors in the guinea-pig ileum revealed by specific binding of fluorescently labelled agonists

Expression of NK-1 and NK-3 tachykinin receptors in pancreatic acinar cells after acute experimental pancreatitis in rats

Characterisation, localisation and expression of porcine TACR1, TACR2 and TACR3 genes

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