Possible role of nitric oxide in 5-hydroxytryptamine-induced increase in vascular permeability in mouse skin

Fujii, Emiko; Irie, Koichiro; Uchida, Yuzo; Tsukahara, Fujiko; Muraki, Takamura

doi:10.1007/bf00178952

Cited by 41 publications

(30 citation statements)

References 19 publications

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“…5-HT is known to induce plasma extravasation by a direct action on the microvasculature in rats (25,26) and to produce vasodilation via 5-HT1 receptors on peripheral blood vessels (27). A recent report (28) suggested that in addition to 5-HT receptors, endogenous nitric oxide is involved in 5-HT-induced increase in vascular permeability in mouse skin. We also showed that ketanserin, LY 53857 and methysergide dose-dependently inhibited ear edema in response to intradermal injection of 5-HT, whereas antagonists for 5-HT1, 5-HT3 and 5-HT4-receptors did not block the edema formation.…”

Section: Discussionmentioning

confidence: 99%

Participation of Serotonin in Capsaicin-Induced Mouse Ear Edema

Inoue

Nagata

Kinoshita

1995

Japanese Journal of Pharmacology

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ABSTRACT-We investigated the involvement of serotonin (5-HT) in mouse ear edema induced by topical application of capsaicin (250 ,ug/ear). Application of capsaicin to the ear caused degranulation of mast cells in skin connective tissue. Capsaicin-induced ear edema was significantly inhibited by preadministration of 5-HT2 receptor antagonists such as ketanserin (2 mg/kg, i.v.) and LY 53857 (1 mg/kg, i.v.), but not 5-HT1-, 5-HT3-and 5-HT4-receptor antagonists. Intradermal injection of a-methyl 5-HT (5-HT2-receptor agonist) and 5-HT into ear skin produced edema formation more potently than 8-OH-DPAT (5-HT1A agonist) and 2-methyl 5-HT (5-HT3 agonist). 5-HT2 antagonists markedly suppressed the edema response to 5-HT and its receptor agonists, whereas any antagonist for 5-HT1, 5-HT3 and 5-HT4-receptors had no effect. Furthermore, 5-HT2-receptor antagonists partly prevented ear edema in response to substance P (SP), a putative mediator of capsaicin-induced edema, and compound 48/80, a releaser of vasoactive amines from mast cells. These results suggest that 5-HT released from mast cells is partly involved in the development of capsaicin-induced mouse ear edema via 5-HT2 receptors in the ear skin.Keywords: Capsaicin, Serotonin (5-HT), Ear edema (mouse), 5-HT receptor, 5-HT-receptor antagonist Capsaicin (8-methyl-N-vanillyl-6-nonenamide), the pungent substance contained in many red peppers, evokes neurogenic inflammatory responses such as axon reflex vasodilation, plasma extravasation and painful sensitization (1). Topical application of capsaicin to the mouse ear produces neurogenic skin inflammation (2, 3), which may be mediated by neuropeptides including substance P (SP) released through activation of primary afferent sensory neurons. Virus and Gebhart (4) have suggested that in addition to SP, serotonin (5-HT) also plays a role in the pharmacological activity of capsaicin. Others have reported that treatment of newborn rats with capsaicin causes an increase in the concentrations of histamine and 5-HT in the rat skin as a result of changes of the mast cell system in response to the permanent degeneration of sensory nerves (5). In fact, evidence exists to indicate that peripheral nerve endings and mast cells are in close spatial and functional association (6 -8). Previous studies have found that methysergide is effective in inhibiting capsaicin-induced mouse ear edema (3). However, clear evidence for the involvement of 5-HT in capsaicin-induced inflammation is lacking.5-HT receptors have been classified into at least four subtypes: 5-HT1, 5-HT2, 5-HT3 and 5-HT4 (9, 10). Among them, 5-HT2 receptors participate in the increase of cutaneous vascular permeability induced by 5-HT in rats (11, 12). 5-HT3 receptors are located on neurons and elicit depolization which results in transmitter release from parasympathetic, sympathetic, sensory and enteric neurons (13). Recent studies have shown that neuropeptides are partly released by mediation of 5-HT3 receptor from capsaicin-sensitive afferent neurons (14). These evidence sugg...

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Section: Discussionmentioning

confidence: 99%

Participation of Serotonin in Capsaicin-Induced Mouse Ear Edema

Inoue

Nagata

Kinoshita

1995

Japanese Journal of Pharmacology

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“…PGE 2 in the supernatant was measured by RIA, and the results were expressed as ng PGE 2 /mg protein/30 min. 2[infi] , LTB 4 , 6-keto PGF 1␣ , histamine, and CINC in cell-free exudates PGE 2 and LTB 4 were measured by enzyme immunoassay and 6-keto PGF 1␣ (as the stable breakdown product of PGI 2 ) by RIA. Results were expressed as quantity (pg) of each eicosanoid in the total volume of cellfree exudate.…”

Section: Cyclooxygenase (Cox) Activity In Inflammatory Cellsmentioning

confidence: 99%

“…Under physiological conditions, NO released from the endothelium regulates vascular tone and maintains vessel patency by helping prevent platelet aggregation and down-regulating adhesion molecule expression (3). However, mediators released during the acute phase of inflammation, including histamine, 5-hydroxytryptamine, bradykinin, platelet-activating factor, and substance P, evoke the release of endothelial NO, causing vasodilatation and vascular permeability, thus facilitating edema formation and trafficking of inflammatory cells (4).…”

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confidence: 99%

Nitric Oxide Synthase Inhibitors Have Opposite Effects on Acute Inflammation Depending on Their Route of Administration

Paul-Clark

Gilroy

Willis

et al. 2001

The Journal of Immunology

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The bulk of published data has shown that NO is proinflammatory. However, there also exists the conflicting notion that NO may be protective during an inflammatory insult. In an attempt to resolve this issue, we have compared the effects on inflammation of a range of NO synthase (NOS) inhibitors given either directly to the site of the inflammatory lesion or systemically. It was found that in the carrageenin-induced pleurisy, a single intrapleural injection of the selective inducible NO inhibitors S-(2-aminoethyl) isothiourea (AE-ITU; 3 and 10 mg/kg) and N-(3-(aminomethyl)-benzyl) acetamidine (1400W; 10 mg/kg) or the selective endothelial cell NOS inhibitor l-N5(1-iminoethyl)-ornithine (10 mg/kg) not only exacerbated inflammation at the very early stages of the lesion (1–6 h), but also prevented inflammatory resolution. By contrast, administering NOS inhibitors systemically ameliorated the severity of inflammation throughout the reaction. To elucidate the mechanisms by which inhibition of NO synthesis locally worsened inflammation, we found an increase in histamine, cytokine-induced neutrophil chemoattractant, superoxide, and leukotriene B4 levels at the inflammatory site. In conclusion, this work shows that the local production of NO is protective by virtue of its ability to regulate the release of typical proinflammatory mediators and, importantly, that NOS inhibitors have differential anti-inflammatory effects depending on their route of administration.

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“…The microvascular permeability of the skin was assessed by an extravasation of PSB as previously described (Fujii et al, 1994). Brie¯y, PSB (50 mg kg 71 ) was injected to the mouse via the tail vein, and 5 min later, LPS (400 mg site 71 ) was subcutaneously (s.c.) administered at the back of the mouse.…”

Section: Determination Of Plasma Leakage In Mouse Skinmentioning

confidence: 99%

Inhibitory effects of cyclic AMP elevating agents on lipopolysaccharide (LPS)‐induced microvascular permeability change in mouse skin

Irie

Fujii

Ishida

et al. 2001

British J Pharmacology

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1 Anti-in¯ammatory e ects of cyclic AMP elevating agents were examined in a mouse model of lipopolysaccharide (LPS)-induced microvascular permeability change. 2 Vascular permeability on the back skin was measured by the local accumulation of Pontamine sky blue (PSB) after subcutaneous injection of LPS (400 mg site 71 ) from Salmonella typhimurium. 3 Dye leakage in the skin was signi®cantly increased 2 h after injection of LPS. This LPS-induced dye leakage was suppressed by phosphodiesterase inhibitors, including pentoxifylline (160 mg kg 71 ), milrinone (5 ± 10 mg kg 71 ), rolipram (0.5 ± 10 mg kg 71 ) and zaprinast (5 ± 10 mg kg 71 ). The dye leakage was also inhibited by b-adrenoceptor agonists, including isoproterenol (0.5 ± 5 mg kg 71 ) and salbutamol (0.05 ± 5 mg kg 71 ), an adenylate cyclase activator, forskolin (5 mg kg 71 ), and a cell permeable cyclic AMP analogue, 8-bromo-cyclic AMP (8-Br-cAMP, 10 mg kg 71 ). 4 LPS caused a transient increase in serum TNF-a level peaking at 1 h after the injection. This increase in serum TNF-a was completely blocked by a pretreatment with pentoxifylline (160 mg kg 71 ), milrinone (5 mg kg 71 ), rolipram (1 mg kg 71 ), zaprinast (10 mg kg 71 ), salbutamol (0.5 mg kg 71 ), forskolin (1 mg kg 71 ) and 8-Br-cAMP (10 mg kg 71 ). 5 LPS caused an increase in serum IL-1a level peaking at 3 h after injection. This increase in serum IL-1a was not signi®cantly suppressed by the cyclic AMP elevating agents. 6 Our study suggests that cyclic AMP elevating agents attenuate LPS-induced microvascular permeability change by suppressing TNF-a up regulation.

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Possible role of nitric oxide in 5-hydroxytryptamine-induced increase in vascular permeability in mouse skin

Cited by 41 publications

References 19 publications

Participation of Serotonin in Capsaicin-Induced Mouse Ear Edema

Participation of Serotonin in Capsaicin-Induced Mouse Ear Edema

Nitric Oxide Synthase Inhibitors Have Opposite Effects on Acute Inflammation Depending on Their Route of Administration

Inhibitory effects of cyclic AMP elevating agents on lipopolysaccharide (LPS)‐induced microvascular permeability change in mouse skin

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