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Susan D Brain

Publications and source records attributed to Susan D Brain.

25 records · Page 2Linked to original sources
PubMed2003

Phoneutria nigriventer spider venom activates 5-HT4 receptors in rat-isolated vagus nerve.

1. The venom of Phoneutria nigriventer spider (PNV) causes intense pain and inflammation following an attack. We have investigated the involvement of capsaicin-sensitive nerve fibres by utilizing an in vitro nerve preparation. Extracellular DC potential recordings were made from the rat-isolated vagus nerve, a preparation that is rich in capsaicin-sensitive, that is, nociceptive, C-fibres. 2. PNV (1-10 microg ml(-1)), capsaicin (0.03-0.3 microM) or 5-hydroxytriptamine (5-HT) (0.3-3 microM) induced dose-dependent depolarizations of vagus nerve fibres. Depolarizing responses to capsaicin were blocked by ruthenium red (RR, 10 microM), but responses to PNV were not. Depolarizing responses to PNV or veratridine (50 microM) were inhibited by tetrodotoxin (TTX, 10 microM), but those to capsaicin were not. This suggests that capsaicin and PNV depolarize the nerve fibres by distinct mechanisms. 3. Depolarization in response to 5-HT (3 microM) was reduced by the 5-HT(3) receptor antagonists Y25130 (0.5 micro M) and tropisetron (10 nM) or, to a lesser extent, by the 5-HT(4) receptor antagonist RS39604 (1 or 10 microM). Depolarizing responses to PNV were not affected significantly by Y25130 or tropisetron, but were blocked by RS39604. 4. These data show that 5-HT(4) receptors play a significant role in the activation of nociceptive sensory nerve fibres by PNV and suggest that this is of importance in the development of the pain and inflammation associated with bites from the P. nigriventer spider.

Action Potentials↗
PubMed2002

Neurokinin B induces oedema formation in mouse lung via tachykinin receptor-independent mechanisms.

The tachykinin neurokinin B (NKB) has been implicated in the hypertension that characterises pre-eclampsia, a condition where tissue oedema is also observed. The ability of NKB, administered intradermally or intravenously, to induce oedema formation (assessed as plasma extravasation) was examined by extravascular accumulation of intravenously injected (125)I-albumin in wild-type and tachykinin NK(1) receptor knockout mice. Intradermal NKB (30-300 pmol) caused dose-dependent plasma extravasation in wild-type (P < 0.05) but not NK(1) knockout mice, indicating an essential role for the NK(1) receptor in mediating NKB-induced skin oedema. Intravenous administration of NKB to wild-type mice produced plasma extravasation in skin, uterus, liver (P < 0.05) and particularly in the lung (P < 0.01). Surprisingly, the same doses of NKB led to plasma extravasation in the lung and liver of NK(1) knockout mice. By comparison, the tachykinin substance P induced only minimal plasma extravasation in the lungs of wild-type mice. The plasma extravasation produced by NKB in the lungs of NK(1) receptor knockout mice was unaffected by treatment with the NK(2) receptor antagonist SR48968 (3 mg kg(-1)), by the NK(3) receptor antagonists SR142801 (3 mg kg(-1)) and SB-222200 (5 mg kg(-1)) or by the cyclo-oxygenase (COX) inhibitor indomethacin (20 mg kg(-1)). L-Nitro-arginine methyl ester (15 mg kg(-1)), an inhibitor of endothelial nitric oxide synthase (eNOS), produced only a partial inhibition. We conclude that NKB is a potent stimulator of plasma extravasation through two distinct pathways: via activation of NK(1) receptors, and via a novel neurokinin receptor-independent pathway specific to NKB that operates in the mouse lung. These findings are in keeping with a role for NKB in mediating plasma extravasation in diseases such as pre-eclampsia.

Animals↗
PubMed2002

Role of kinins and sensory neurons in the rat pleural leukocyte migration induced by Phoneutria nigriventer spider venom.

The leukocyte migration induced by Phoneutria nigriventer spider venom (PNV) has been investigated in rats using the pleurisy model. Intrapleural injection of PNV (10-100 microg/cavity) caused a dose- and time-dependent leukocyte accumulation. The bradykinin B(2) receptor antagonist Hoe 140 (0.5 mg/kg) substantially inhibited PNV-induced cell accumulation, whereas the angiotensin-converting enzyme inhibitor captopril (2 mg/kg) potentiated by 80% this effect. The non-specific kallikrein inhibitor aprotinin and the plasma kallikrein inhibitor soybean trypsin inhibitor greatly reduced PNV-induced leukocyte migration, whereas the selective tissue kallikrein inhibitor P(ac)-F-S-R-EDDnp failed to affect PNV-induced responses. Treatment of rats with capsaicin (50 mg/kg) at the neonatal stage resulted in 67% inhibition of the PNV-induced cell migration. The neurokinin NK(1) receptor antagonist SR140333, but not the NK(2) receptor antagonist SR48968, reduced by 55% venom-induced cell accumulation. We conclude that bradykinin generation is involved in the PNV-induced pleural leukocyte migration in rats, where it can directly activate sensory nerves contributing to a neurogenic inflammatory mechanism.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2002

Interaction between interleukin 1beta and endogenous neurokinin 1 receptor agonists in mediating plasma extravasation and neutrophil accumulation in the cutaneous microvasculature of the rat.

Interleukin 1beta (IL-1beta) is a potent mediator of neutrophil accumulation. Antidromic stimulation of the rat saphenous nerve leads to neurogenic oedema formation mediated by endogenous tachykinins. Here, we have investigated links between IL-1beta and the tachykinin 1 (NK(1)) receptors in microvascular events in rat skin. Saphenous nerve-induced plasma extravasation was not modulated by skin pretreatment with IL-1beta (3 pmol/site intradermally). In addition, the long-lasting antidromic electrical stimulation did not induce significant neutrophil accumulation in naive rat skin. By comparison, the effect of IL-1beta-induced neutrophil accumulation was significantly potentiated by co-stimulation of the ipsilateral saphenous nerve; an effect prevented by an NK(1) receptor antagonist (SR140333, 480 nmol/kg, i.v.). We conclude that IL-1beta-induced neutrophil accumulation can be influenced in a pro-inflammatory manner by ongoing neurogenic inflammation, of relevance to the sensory nerve input that occurs during ongoing inflammatory disease.

Animals↗
PubMed2002

Cellular pathology changes in rat skin following intradermal injection of nerve growth factor: neutrophil-dependent and -independent events.

Nerve growth factor (NGF) regulates the survival and development of specific populations of neurones and is involved in wound healing. A further area of study relating to the role of neurotrophins in the mature animal has concerned the possibility that NGF may be a pivotal mediator of inflammation and pain. It has previously been shown that injection of intradermal NGF can result in a neutrophil-dependent hyperalgesia in the rat. The purpose of the present study was to examine the pathological consequence of NGF injected intradermally into mature rat skin and to examine further the role of neutrophils. Standard histopathology techniques (H & E) were employed to determine inflammatory cell counts. Circulating neutrophils were depleted using an anti-rat neutrophil antiserum and results were compared to treatment with vehicle controls. Saline-pretreated rats exhibited normal circulating neutrophil numbers and the dorsal skin showed a significant increase of neutrophil and macrophages at 3 and 5 h and lymphocytes at 5 h after NGF treatment. By comparison, skin sites from neutrophil-depleted rats did not demonstrate a significant increase in neutrophil and macrophage accumulation after NGF administration. All NGF-treated sites, independent of pretreatment, demonstrated abnormal muscle fibre morphology and proliferation of the muscle sarcolemmal nuclei after NGF injection, indicative of tissue injury. In addition, oedema and some fibroplasia were also noted. Furthermore, fibrin production was increased at 3 and 5 h after NGF administration. It is suggested that NGF has a damaging effect on rat muscle which is independent of accumulating neutrophil and other inflammatory cells. In conclusion, the findings indicate a link between NGF-induced neutrophil and macrophage accumulation, as the increase in dermal macrophages was not observed in neutrophil-depleted rats. The results also suggest that NGF can have a profound effect on rat muscle and that this effect may be related to muscle regeneration.

Animals↗
PubMed2002

Evidence of a role for NK1 and CGRP receptors in mediating neurogenic vasodilatation in the mouse ear.

The aims of this study were to develop a technique to measure blood flow in the mouse ear and to investigate the nature of the vasodilator mediator(s) involved in the response to capsaicin. The response to capsaicin, applied topically, was investigated in anaesthetized CD1 or Sv129+C57BL/6 wild-type (+/+) or NK(1) receptor knockout mice (-/-). Blood flow was assessed by laser Doppler flowmetry and oedema formation by (125)I-albumin accumulation. Capsaicin induced significant increases in blood flow (0.2 - 200 microg in 20 microl) and oedema (2 - 200 microg in 20 microl). The oedema response was absent in NK(1)-/- mice and NK(1)+/+mice treated with the selective NK(1) receptor antagonist SR140333 (480 nmol kg(-1)) as expected. Furthermore, the capsaicin-evoked increase in blood flow was significantly potentiated in the knockout mice (203% of wild-type response, P<0.05) and wild-type mice treated with SR140333 (201%, P<0.05). The CGRP receptor antagonist CGRP(8 - 37) (400 nmol kg(-1)) had no effect on capsaicin-induced blood flow in NK(1)+/+mice but abolished the increased blood flow to capsaicin in NK(1)-/-, and NK(1)+/+wild-type mice pre-treated with SR140333. The results indicate that neurogenic vasodilatation can be measured in the mouse ear. The capsaicin-induced increased blood flow involves activation of, and possible interactions between, both NK(1) and CGRP(1) receptors.

Animals↗