Role of Substance P and Bradykinin in Acute Pancreatitis Induced by Secretory Phospholipase A2

Camargo, Enilton A.; Ferreira, Tatiane; Ribela, M.T.C.P.; Nucci, Gilberto De; Landucci, Elen C.T.; Antunes, Edson

doi:10.1097/mpa.0b013e3185d9b9b

Cited by 19 publications

(18 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For this purpose, tissues were dried by overnight incubation at 90°C. The plasma protein extravasation was measured by the accumulation of intravenously injected [ 125 I]‐human serum albumin (HSA 2.5μCi rat −1 ; Camargo et al, 2005, 2008a). A blood sample was collected and centrifuged at 8000 g for 10 min to obtain a plasma sample.…”

Section: Methodsmentioning

confidence: 99%

Abdominal hyperalgesia in secretory phospholipase A₂‐induced rat pancreatitis: Distinct roles of NK₁ receptors

Camargo

Zanoni

Toyama

et al. 2011

European Journal of Pain

View full text Add to dashboard Cite

We investigated the potential of secretory phospholipase A(2) (sPLA(2))-induced pancreatitis to promote abdominal hyperalgesia, as well as to depolarize sensory fibres in vitro using a grease-gap technique. Pancreatitis was induced by the injection of sPLA(2) from Crotalus durissus terrificus (sPLA(2)Cdt, 300μgkg(-1)) venom into the common bile duct of rats. Pancreatic inflammatory signs, serum amylase levels and abdominal hyperalgesia were evaluated in rats treated or not with SR140333, a tachykinin NK(1) receptor antagonist. Injection of sPLA(2)Cdt caused pancreatic oedema formation and increased pancreatic neutrophil infiltration and serum amylase at 4h, which returned to normality by 24h, except for the neutrophil infiltration, which was still increased at this time point. Animals injected with sPLA(2) exhibited a lower withdrawal threshold to electronic von Frey stimulation in the upper abdominal region at 4h, but not 24h, post-injection when compared with saline-injected rats. Pre-treatment of animals with SR140333 significantly reduced the sPLA(2)Cdt-induced abdominal hyperalgesia, without affecting the other parameters. Neither sPLA(2)Cdt nor sPLA(2) from Naja mocambique mocambique venom depolarized capsaicin-sensitive sensory fibres from rat vagus nerve, but they decreased the propagated compound action potentials in both A and C fibres. These data show for the first time that NK(1) receptors play an important role in the early abdominal hyperalgesia in a rat model of sPLA(2)-induced pancreatitis, suggesting that these receptors are of importance in the development of pain in the pancreatitis condition. We also provide evidence that sPLA(2)s do not directly depolarize sensory fibres in vitro.

show abstract

Section: Methodsmentioning

confidence: 99%

Abdominal hyperalgesia in secretory phospholipase A₂‐induced rat pancreatitis: Distinct roles of NK₁ receptors

Camargo

Zanoni

Toyama

et al. 2011

European Journal of Pain

View full text Add to dashboard Cite

show abstract

“…A number of PLA2s exert strong myotoxic effects which often lead to severe necrosis (Harris and Maltin, 1982;Gutierrez and Ownby, 2003), and many of these toxins also promote inflammation, including edema formation, cytokine production and leukocyte recruitment, pain by inducing thermal allodynia and mechanical hyperalgesia, paralysis through block of neuromuscular transmission and intensify hemorrhage by inhibiting coagulation (Table 1) (Camara et al, 2003;Chacur et al, 2003;Camargo et al, 2008;Teixeira et al, 2011;Lomonte and Rangel, 2012;Harris and Scott-Davey, 2013;Casais-E-Silva et al, 2016;Costa et al, 2017;Zambelli et al, 2017b;Zhang et al, 2017). Neurotoxic effects caused by these toxins, as well as some of their proinflammatory effects, occurs via the modulation of pre-synaptic terminals as well as sensory nerveendings (Camara et al, 2003;Harris and Scott-Davey, 2013;Sribar et al, 2014;Zhang et al, 2017).…”

Section: Phospholipases (Pla2s)mentioning

confidence: 99%

“…The inflammation induced by PLA2s has non-neurogenic and neurogenic (substance-P dependent) components (Camara et al, 2003;Camargo et al, 2008;Costa et al, 2017;Zhang et al, 2017). The non-neurogenic component is mostly caused by the hydrolysis of membrane lipids that generate potent pro-inflammatory lipid mediators .…”

Section: Phospholipases (Pla2s)mentioning

confidence: 99%

Multifunctional Toxins in Snake Venoms and Therapeutic Implications: From Pain to Hemorrhage and Necrosis

et al. 2019

View full text Add to dashboard Cite

Animal venoms have evolved over millions of years for prey capture and defense from predators and rivals. Snake venoms, in particular, have evolved a wide diversity of peptides and proteins that induce harmful inflammatory and neurotoxic effects including severe pain and paralysis, hemotoxic effects, such as hemorrhage and coagulopathy, and cytotoxic/myotoxic effects, such as inflammation and necrosis. If untreated, many envenomings result in death or severe morbidity in humans and, despite advances in management, snakebite remains a major public health problem, particularly in developing countries. Consequently, the World Health Organization recently recognized snakebite as a neglected tropical disease that affects ∼2.7 million p.a. The major protein classes found in snake venoms are phospholipases, metalloproteases, serine proteases, and three-finger peptides. The mechanisms of action and pharmacological properties of many snake venom toxins have been elucidated, revealing a complex multifunctional cocktail that can act synergistically to rapidly immobilize prey and deter predators. However, despite these advances many snake toxins remain to be structurally and pharmacologically characterized. In this review, the multifunctional features of the peptides and proteins found in snake venoms, as well as their evolutionary histories, are discussed with the view to identifying novel modes of action and improving snakebite treatments.

show abstract

“…Other mediators were with some success targeted in experimental AP. In severe porcine AP and in various rat models of AP, pretreatment with the inhibitor of bradykinin B2 receptor (icatibant) showed beneficial effects [91,92,93,94]. Endothelin-1, a potent vasoconstrictor, was shown to be up-regulated in pancreatic endothelial cells by inflammatory stimuli, including cytokines, thrombin, and trypsin, which was associated with impaired splanchnic microcirculation in SAP [95].…”

Section: Vascular Involvement In Acute Pancreatitismentioning

confidence: 99%

The Interplay between Inflammation, Coagulation and Endothelial Injury in the Early Phase of Acute Pancreatitis: Clinical Implications

Dumnicka

Maduzia

Ceranowicz

et al. 2017

IJMS

160

113

View full text Add to dashboard Cite

Acute pancreatitis (AP) is an inflammatory disease with varied severity, ranging from mild local inflammation to severe systemic involvement resulting in substantial mortality. Early pathologic events in AP, both local and systemic, are associated with vascular derangements, including endothelial activation and injury, dysregulation of vasomotor tone, increased vascular permeability, increased leukocyte migration to tissues, and activation of coagulation. The purpose of the review was to summarize current evidence regarding the interplay between inflammation, coagulation and endothelial dysfunction in the early phase of AP. Practical aspects were emphasized: (1) we summarized available data on diagnostic usefulness of the markers of endothelial dysfunction and activated coagulation in early prediction of severe AP; (2) we reviewed in detail the results of experimental studies and clinical trials targeting coagulation-inflammation interactions in severe AP. Among laboratory tests, d-dimer and angiopoietin-2 measurements seem the most useful in early prediction of severe AP. Although most clinical trials evaluating anticoagulants in treatment of severe AP did not show benefits, they also did not show significantly increased bleeding risk. Promising results of human trials were published for low molecular weight heparin treatment. Several anticoagulants that proved beneficial in animal experiments are thus worth testing in patients.

show abstract

Role of Substance P and Bradykinin in Acute Pancreatitis Induced by Secretory Phospholipase A2

Abstract: We concluded that NK-1 and B2 receptors can regulate important steps in the local and remote inflammation during acute pancreatitis induced by sPLA2.

Cited by 19 publications

References 47 publications

Abdominal hyperalgesia in secretory phospholipase A₂‐induced rat pancreatitis: Distinct roles of NK₁ receptors

Abdominal hyperalgesia in secretory phospholipase A₂‐induced rat pancreatitis: Distinct roles of NK₁ receptors

Multifunctional Toxins in Snake Venoms and Therapeutic Implications: From Pain to Hemorrhage and Necrosis

The Interplay between Inflammation, Coagulation and Endothelial Injury in the Early Phase of Acute Pancreatitis: Clinical Implications

Contact Info

Product

Resources

About

Role of Substance P and Bradykinin in Acute Pancreatitis Induced by Secretory Phospholipase A2

Abstract: We concluded that NK-1 and B2 receptors can regulate important steps in the local and remote inflammation during acute pancreatitis induced by sPLA2.

Cited by 19 publications

References 47 publications

Abdominal hyperalgesia in secretory phospholipase A2‐induced rat pancreatitis: Distinct roles of NK1 receptors

Abdominal hyperalgesia in secretory phospholipase A2‐induced rat pancreatitis: Distinct roles of NK1 receptors

Multifunctional Toxins in Snake Venoms and Therapeutic Implications: From Pain to Hemorrhage and Necrosis

The Interplay between Inflammation, Coagulation and Endothelial Injury in the Early Phase of Acute Pancreatitis: Clinical Implications

Contact Info

Product

Resources

About

Abdominal hyperalgesia in secretory phospholipase A₂‐induced rat pancreatitis: Distinct roles of NK₁ receptors

Abdominal hyperalgesia in secretory phospholipase A₂‐induced rat pancreatitis: Distinct roles of NK₁ receptors