Substance P inhibits pancreatic exocrine secretion via a neural mechanism

Kirkwood, Kimberly S.; Kim, Edward H.; He, Xiao Ying; Calaustro, Edna Q.; Domush, Christopher; Yoshimi, Shandra K.; Grady, Eileen F.; Maa, John; Bunnett, Nigel W.; Debas, Haile T.

doi:10.1152/ajpgi.1999.277.2.g314

Cited by 17 publications

(13 citation statements)

References 37 publications

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“…Previous data (2) show that SP levels and NK-1 receptors in pancreatic acinar cells are upregulated during experimental pancreatitis in mice. In addition, NK-1 receptor deletion or antagonism protects mice against pancreatitis (3,9,15). SP-induced activation of the NK-1 receptor is an important proinflammatory step also in rat acute pancreatitis.…”

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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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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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“…The choice of biologically active substances in the co-localization study was justified by their activities in relation to the mammalian pancreas. For example, SP was found to inhibit amylase release and induce pancreatic juice flow in the rat (KIRKWOOD et al, 1999). GAL is known to inhibit amylase and insulin secretion (AHREN et al, 1988;DUNNING et al, 1986), reduce pancreatic vascular perfusion (BROOKE-SMITHet al, 2008) and to increase pancreatic juice secretion rate (BHANDARI et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Leucine-enkephalin is co-expressed with substance P, galanin and somatostatin in the ovine pancreas

2017

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Leucine-enkephalin (Leu-Enk) is an endogenous opioid peptide that binds to opioid receptors. Leu-Enk is widely distributed in the central and peripheral nervous system. The aim of the present immunofluorescence study was to examine the distribution of Leu-Enk-immunoreactive (IR) neuronal elements in the ovine pancreas. Using double immunohistochemical staining, the co-localization of Leu-Enk with galanin, somatostatin and substance P was also studied. In the intrapancreatic ganglia, immunoreactivity to Leu-Enk was found in 64.9 ± 1.7% of neurons. Small arterioles and the ductal system were innervated by numerous Leu-Enk-IR nerve terminals. Moderate Leu-Enk-IR nerve fibres surrounded the islets of Langerhans but none of them penetrated into spaces between endocrine cells. In 66.7 ± 4.3% of Leu-Enk-immunoreactive intrapancreatic neurons, expression of galanin was found. A statistically smaller subpopulation of Leu-Enk-IR intrapancreatic neurons (37.4 ± 6.2%) exhibited immunoreactivity to SP. The expression of somatostatin was detected in the relatively smallest group (21.2 ± 3.8%) of Leu-Enk-positive intrapancreatic neurons. Co-expression of Leu-Enk and SP was detected in nerve terminals encircling the pancreatic small arterioles, connective tissue and ducts. LeuEnk-positive nerve fibres around the islets of Langerhans were not immunoreactive for SP. None of the Leu-ENK-positive nerve fibres around the islets of Langerhans co-stored somatostatin. In general, there was also no co-localization between Leu-Enk and somatostatin in nerve terminals supplying small arterioles and veins. Coexpression of GAL and Leu-Enk was observed well in nerve fibres encircling the blood vessels, but not in nerve fibres of the connective tissue. We conclude that abundant immunoreactivity to Leu-Enk in the ovine pancreas and the co-localization of Leu-Enk with other regulatory neuropeptides may reflect the possible involvement of Leu-Enk as a regulator of the exocrine and endocrine pancreatic functions, as well as in regulation of pancreatic blood flow.

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“…Exogenous substance P dose-dependently inhibited cholecystokinininduced amylase release and secretin induced juice flow via the pancreatic duct in isolated, perfused rat pancreas (33). The effects of SP were partially blocked by NK1R and NK2R receptors (33). These observations were suggested to be mediated by a neural pathway and involve activation of the neurokinin-1 receptor (33).…”

Section: Effects Of Substance P On Pancreatic Exocrine Secretionmentioning

confidence: 94%

Section: Effects Of Substance P On Pancreatic Exocrine Secretionmentioning

confidence: 95%

“…The effects of SP were partially blocked by NK1R and NK2R receptors (33). These observations were suggested to be mediated by a neural pathway and involve activation of the neurokinin-1 receptor (33). In contrast, Schmidt et al showed that substance P stimulation of the pancreas stimulates pancreatic exocrine secretion in isolated porcine pancreas, and was attenuated by NK1R antagonists (64).…”

Section: Effects Of Substance P On Pancreatic Exocrine Secretionmentioning

confidence: 98%

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Substance P (SP)

Bhatia¹

The Pancreapedia: Exocrine Pancreas Knowledge Base

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Substance P inhibits pancreatic exocrine secretion via a neural mechanism

Cited by 17 publications

References 37 publications

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

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

Leucine-enkephalin is co-expressed with substance P, galanin and somatostatin in the ovine pancreas

Substance P (SP)

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