scholarly journals Mechanisms Mediating Porphyromonas gingivalis Gingipain RgpA-Induced Oral Mucosa Inflammation In Vivo

2001 ◽  
Vol 69 (2) ◽  
pp. 1199-1201 ◽  
Author(s):  
Israel Rubinstein ◽  
Jan Potempa ◽  
James Travis ◽  
Xiao-Pei Gao
Keyword(s):  
Oral Mucosa ◽  
Porphyromonas Gingivalis ◽  
Proteinase Inhibitors ◽  
Cheek Pouch ◽  
Induced Responses ◽  
Hamster Cheek Pouch ◽  
Plasma Exudation ◽  
Significant Concentration

ABSTRACT Suffusion of gingipain RgpA (GRgpA) elicited a significant concentration-dependent increase in the clearance of macromolecules from in situ hamster cheek pouch which was attenuated by NPC 17647, a selective bradykinin B2 receptor antagonist. Leupeptin and a mixture of proteinase inhibitors also attenuated GRgpA-induced responses. These data indicate that GRgpA elicits plasma exudation from in situ oral mucosa in a catalytic site-dependent fashion by elaborating bradykinin.

Neutral endopeptidase modulates substance P-induced vasodilation in vivo

1995 ◽  
Vol 78 (2) ◽  
pp. 562-568 ◽  
Author(s):  
X. P. Gao ◽  
I. Rubinstein
Keyword(s):  
Substance P ◽  
Oral Mucosa ◽  
Intravital Microscopy ◽  
Neutral Endopeptidase ◽  
Cheek Pouch ◽  
Induced Responses ◽  
Hamster Cheek Pouch ◽  
Arteriolar Diameter ◽  
Significant Concentration

The purpose of this study was to investigate whether neutral endopeptidase (NEP; EC 3.4.24.11) modulates substance P-induced vasodilation in the oral mucosa in vivo. Using intravital microscopy, we measured the diameter of second-order arterioles (44–70 microns) in the hamster cheek pouch during suffusion of capsaicin and substance P. We found that capsaicin (0.1 and 10.0 nM) induced significant concentration-dependent vasodilations (13 +/- 4 and 39 +/- 7% increase from baseline, respectively; P < 0.05) that were significantly potentiated by phosphoramidon (10.0 nM), a selective NEP inhibitor (35 +/- 15 and 61 +/- 12% increase from baseline, respectively; P < 0.05). Substance P (0.1 and 10.0 nM) also induced significant concentration-dependent vasodilations (7 +/- 3 and 25 +/- 8% increase from baseline, respectively; P < 0.05) that were mediated by the COOH-terminal of the molecule. Substance P-induced responses were significantly potentiated by phosphoramidon (34 +/- 9 and 53 +/- 10% increase from baseline, respectively; P < 0.05) and thiorphan (10.0 microM), a selective NEP inhibitor (44 +/- 11 and 53 +/- 10% increase from baseline, respectively; P < 0.05). Substance P-(1–9) had no significant effects on arteriolar diameter. Suffusion of captopril, leupeptin, Bestatin, and DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid together had no significant effects on substance P-induced vasodilation. Phosphoramidon did not potentiate nitroglycerin-induced vasodilation. These data indicate that NEP modulates substance P-induced vasodilation in the hamster cheek pouch in vivo. We suggest that any decrease in tissue NEP activity may amplify neurogenic vasodilation in the oral mucosa.

Loop diuretics attenuate bradykinin-induced increase in clearance of macromolecules in the oral mucosa

1996 ◽  
Vol 80 (3) ◽  
pp. 818-823 ◽  
Author(s):  
X. P. Gao ◽  
J. M. Conlon ◽  
J. K. Vishwanatha ◽  
R. A. Robbins ◽  
I. Rubinstein
Keyword(s):  
Oral Mucosa ◽  
Fluorescein Isothiocyanate ◽  
Loop Diuretics ◽  
Cheek Pouch ◽  
Site Formation ◽  
Induced Responses ◽  
Vasomotor Tone ◽  
Hamster Cheek Pouch ◽  
Significant Concentration

The purpose of this study was to determine whether loop diuretics attenuate bradykinin-induced increase in clearance of macromolecules in the oral mucosa in situ and, if so, to start to determine the mechanisms that mediated these responses. By using intravital microscopy, we found that bradykinin induced a significant concentration-dependent increase in fluorescein isothiocyanate-labeled dextran (mol mass 70 kDa) leaky site formation in the hamster cheek pouch. These responses were significantly attenuated by topical application of two structurally distinct loop diuretics, furosemide and ethacrynic acid, onto the cheek pouch (P < 0.05). Hydrochlorothiazide, a nonloop diuretic, had no significant effects on bradykinin-induced responses. Furosemide had no significant effects on adenosine-induced leaky site formation. Application of bradykinin after furosemide, but not after hydrochlorothiazide, was associated with a significant concentration-dependent decrease in bradykinin-like immunoreactivity in the cheek pouch suffusate (P < 0.05). Prostaglandins and changes in vasomotor tone did not modulate the effects of furosemide on bradykinin-induced responses. These data indicate that loop diuretics attenuate bradykinin-induced increase in clearance of macromolecules in the oral mucosa in a specific fashion, probably by amplifying local bradykinin catabolism. We suggest that topical loop diuretics could be useful in the treatment of oral mucosa inflammation elicited by bradykinin.

Smokeless tobacco-exposed oral keratinocytes increase macromolecular efflux from the in situ oral mucosa

1998 ◽  
Vol 274 (1) ◽  
pp. R104-R111 ◽  
Author(s):  
Israel Rubinstein ◽  
Xiao-Pei Gao ◽  
Sergei Pakhlevaniants ◽  
Dolphine Oda
Keyword(s):  
Oral Mucosa ◽  
Smokeless Tobacco ◽  
Fluorescein Isothiocyanate ◽  
Cheek Pouch ◽  
Oral Keratinocytes ◽  
Hamster Cheek Pouch ◽  
Hoe 140 ◽  
Significant Concentration

The purpose of this study was to determine whether supernatants of cultured human oral keratinocytes (HOK) exposed to an aqueous extract of smokeless tobacco (STE) increase macromolecular efflux from the oral mucosa in vivo and, if so, whether bradykinin mediates in part this response. Subconfluent monolayers of HOK were incubated with STE or media, and supernatants were collected 24, 48, and 72 h thereafter. Using intravital microscopy, we found that suffusion of supernatants of STE- but not media-exposed HOK elicited significant concentration- and time-dependent increases in efflux of fluorescein isothiocyanate-labeled dextran (mol mass 70 kDa) from the in situ hamster cheek pouch ( P < 0.05). These effects were significantly attenuated by HOE-140 and NPC-17647 but not by des-Arg9,[Leu8]-bradykinin. Proteolytic activity was increased in supernatants of STE- but not media-exposed HOK. However, a mixture of leupeptin, Bestatin, anddl-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid had no significant effects on HOK supernatant-induced responses. Collectively, these data suggest that oral keratinocytes modulate smokeless tobacco-induced increase in macromolecular efflux from the in situ oral mucosa in part by elaborating proteases that may account for local bradykinin production.

Tannic acid elicits neurogenic plasma exudation from the in situ hamster cheek pouch

1998 ◽  
Vol 274 (1) ◽  
pp. R237-R242
Author(s):  
Xiao-Pei Gao
Keyword(s):  
Tannic Acid ◽  
Biosynthetic Pathway ◽  
Fluorescein Isothiocyanate ◽  
Cheek Pouch ◽  
Site Formation ◽  
Hamster Cheek Pouch ◽  
Plasma Exudation ◽  
Synthase Inhibitor

The purpose of this study was to determine whether tannic acid elicits neurogenic plasma exudation from the oral mucosa in vivo and, if so, whether this response is transduced in part by thel-arginine-nitric oxide (NO) biosynthetic pathway. Using intravital microscopy, we found that suffusion of tannic acid elicits significant concentration-dependent leaky site formation and increase in clearance of fluorescein isothiocyanate-dextran (molecular mass 70 kDa) from the in situ hamster cheek pouch ( P < 0.05). These effects are significantly attenuated by two selective, but structurally distinct, nonpeptide neurokinin-1 (NK1) receptor antagonists, CP-96,345 and RP-67580, but not by CP-96,344, the 2R,3R enantiomer of CP-96,345. N G-nitrol-arginine methyl ester (l-NAME), an NO synthase inhibitor, but notd-NAME, significantly attenuates tannic acid-induced responses.l-Arginine, but notd-arginine, reverses the attenuating effects of l-NAME. We conclude that tannic acid elicitsl-arginine-NO biosynthetic pathway-dependent neurogenic plasma exudation from the in situ hamster cheek pouch.

Exogenous calmodulin potentiates vasodilation elicited by phospholipid-associated VIP in vivo

1999 ◽  
Vol 276 (5) ◽  
pp. R1359-R1365 ◽  
Author(s):  
Hiroyuki Ikezaki ◽  
Manisha Patel ◽  
Hayat Önyüksel ◽  
Syed R. Akhter ◽  
Xiao-Pei Gao ◽  
...  
Keyword(s):  
Active Sites ◽  
Calcium Ionophore ◽  
Cheek Pouch ◽  
Induced Responses ◽  
Hamster Cheek Pouch ◽  
Sterically Stabilized Liposomes ◽  
Extracellular Calmodulin ◽  
Peripheral Microcirculation

The purpose of this study was to determine whether exogenous calmodulin potentiates vasoactive intestinal peptide (VIP)-induced vasodilation in vivo and, if so, whether this response is amplified by association of VIP with sterically stabilized liposomes. Using intravital microscopy, we found that calmodulin suffused together with aqueous and liposomal VIP did not potentiate vasodilation elicited by VIP in the in situ hamster cheek pouch. However, preincubation of calmodulin with liposomal, but not aqueous, VIP for 1 and 2 h and overnight at 4°C before suffusion significantly potentiated vasodilation ( P < 0.05). Calmodulin-induced responses were significantly attenuated by calmidazolium, trifluoperazine, and N G-nitro-l-arginine methyl ester (l-NAME) but notd-NAME. The effects ofl-NAME were reversed byl- but notd-arginine. Indomethacin had no significant effects on calmodulin-induced responses. Calmodulin had no significant effects on adenosine-, isoproterenol-, acetylcholine-, and calcium ionophore A-23187-induced vasodilation. Collectively, these data indicate that exogenous calmodulin amplifies vasodilation elicited by phospholipid-associated, but not aqueous, VIP in the in situ peripheral microcirculation in a specific, calmodulin active sites-, and nitric oxide-dependent fashion. We suggest that extracellular calmodulin, phospholipids, and VIP form a novel functionally coordinated class of endogenous vasodilators.

scholarly journals Dexamethasone attenuates acute macromolecular efflux increase evoked by smokeless tobacco extract

1999 ◽  
Vol 87 (2) ◽  
pp. 619-625 ◽  
Author(s):  
Xiao-Pei Gao ◽  
Syed R. Akhter ◽  
Hiroyuki Ikezaki ◽  
Dennis Hong ◽  
Israel Rubinstein
Keyword(s):  
Oral Mucosa ◽  
Smokeless Tobacco ◽  
Fluorescein Isothiocyanate ◽  
Cheek Pouch ◽  
Site Formation ◽  
Hamster Cheek Pouch ◽  
Acute Increase ◽  
Tobacco Extract

The purpose of this study was to determine whether dexamethasone attenuates the acute increase in macromolecular efflux from the oral mucosa elicited by an aqueous extract of smokeless tobacco (STE) in vivo, and, if so, whether this response is specific. Using intravital microscopy, we found that 20-min suffusion of STE elicited significant, concentration-related leaky site formation and an increase in clearance of fluorescein isothiocyanate-labeled dextran (FITC-dextran; mol mass 70 kDa) from the in situ hamster cheek pouch ( P < 0.05). This response was significantly attenuated by dexamethasone (10 mg/kg iv). Dexamethasone also attenuated the bradykinin-induced leaky site formation and the increase in clearance of FITC-dextran from the cheek pouch. However, it had no significant effects on adenosine-induced responses. Dexamethasone had no significant effects on baseline arteriolar diameter and on bradykinin-induced vasodilation in the cheek pouch. Collectively, these data indicate that dexamethasone attenuates, in a specific fashion, the acute increase in macromolecular efflux from the in situ oral mucosa evoked by short-term suffusion of STE. We suggest that corticosteroids mitigate acute oral mucosa inflammation elicited by smokeless tobacco.

Dexamethasone attenuates grain sorghum dust extract-induced increase in macromolecular efflux in vivo

1999 ◽  
Vol 86 (5) ◽  
pp. 1603-1609 ◽  
Author(s):  
Syed R. Akhter ◽  
Hiroyuki Ikezaki ◽  
Xiao-Pei Gao ◽  
Israel Rubinstein
Keyword(s):  
Substance P ◽  
Grain Sorghum ◽  
Cheek Pouch ◽  
Site Formation ◽  
Hamster Cheek Pouch ◽  
Arteriolar Diameter ◽  
Dust Extract ◽  
Significant Concentration

The purpose of this study was to determine whether dexamethasone attenuates grain sorghum dust extract-induced increase in macromolecular efflux from the in situ hamster cheek pouch and, if so, whether this response is specific. By using intravital microscopy, we found that an aqueous extract of grain sorghum dust elicited significant, concentration-dependent leaky site formation and increase in clearance of FITC-labeled dextran (FITC-dextran; mol mass, 70 kDa) from the in situ hamster cheek pouch ( P < 0.05). This response was significantly attenuated by dexamethasone (10 mg/kg iv). Dexamethasone also attenuated substance P-induced leaky site formation and increase in clearance of FITC-dextran from the cheek pouch but had no significant effects on adenosine-induced responses. Dexamethasone had no significant effects on arteriolar diameter in the cheek pouch. On balance, these data indicate that dexamethasone attenuates grain sorghum dust extract- and substance P-induced increases in macromolecular efflux from the in situ hamster cheek pouch in a specific fashion.

Hog barn dust extract increases macromolecular efflux from the hamster cheek pouch

2006 ◽  
Vol 101 (1) ◽  
pp. 128-134
Author(s):  
Israel Rubinstein ◽  
Susanna G. Von Essen
Keyword(s):  
Upper Airway ◽  
Cheek Pouch ◽  
Site Formation ◽  
Short Term ◽  
Hamster Cheek Pouch ◽  
Short Term Exposure ◽  
Plasma Exudation ◽  
Dust Extract ◽  
Significant Concentration

The purpose of this study was to determine whether short-term exposure to an aqueous extract of hog barn dust increases macromolecular efflux from the intact hamster cheek pouch and, if so, to begin to determine the mechanism(s) underlying this response. By using intravital microscopy, we found that suffusion of hog barn dust extract onto the intact hamster cheek pouch for 60 min elicited a significant, concentration-dependent leaky site formation and increase in clearance of FITC-labeled dextran (molecular mass, 70 kDa). This response was significantly attenuated by suffusion of catalase (60 U/ml), but not by heat-inactivated catalase, and by pretreatment with dexamethasone (10 mg/kg iv) ( P < 0.05). Catalase had no significant effects on adenosine-induced increase in macromolecular efflux from the cheek pouch. Suffusion of hog barn dust extract had no significant effects on arteriolar diameter in the cheek pouch. Taken together, these data indicate that hog barn dust extract increases macromolecular efflux from the in situ hamster cheek pouch, in part, through local elaboration of reactive oxygen species that are inactivated by catalase. This response is specific and attenuated by corticosteroids. We suggest that plasma exudation plays an important role in the genesis of upper airway dysfunction evoked by short-term exposure to hog barn dust.

Peptidases modulate bradykinin-induced arteriolar dilation in the hamster cheek pouch

1994 ◽  
Vol 266 (1) ◽  
pp. H93-H98 ◽  
Author(s):  
X. P. Gao ◽  
P. Anding ◽  
R. A. Robbins ◽  
S. I. Rennard ◽  
I. Rubinstein
Keyword(s):  
Proteinase Inhibitors ◽  
Neutral Endopeptidase ◽  
Cheek Pouch ◽  
Induced Responses ◽  
Hamster Cheek Pouch ◽  
Before And After ◽  
Peripheral Microcirculation ◽  
Membrane Bound ◽  
Arteriolar Diameter

The purpose of this study was to investigate whether angiotensin-converting enzyme (ACE; EC 3.4.15.1) and neutral endopeptidase (NEP; EC 3.4.24.11), two membrane-bound metalloenzymes that are widely distributed in the peripheral microcirculation and degrade kinins very effectively, modulate bradykinin-induced arteriolar dilation in vivo. Using intravital microscopy, we measured diameter of second-order arterioles in the hamster cheek pouch during suffusion of bradykinin (0.1–10.0 microM) before and after topical application of captopril (10.0 microM) and phosphoramidon (10.0 nM). We found that each inhibitor significantly potentiated bradykinin-induced increase in arteriolar diameter (P < 0.05). Suffusion of other proteinase inhibitors (excluding ACE and NEP inhibitors) had no significant effect on bradykinin-induced responses. Captopril and phosphoramidon did not potentiate isoproterenol (0.1 microM)-induced arteriolar dilation in the cheek pouch. Collectively, these data indicate that ACE and NEP each plays an important role in regulating bradykinin-induced vasorelaxation in the peripheral microcirculation in vivo.

scholarly journals Methotrexate potentiates bradykinin-induced increase in macromolecular efflux from the hamster oral mucosa

1997 ◽  
Vol 273 (4) ◽  
pp. R1254-R1262 ◽  
Author(s):  
Xiao-Pei Gao ◽  
Israel Rubinstein
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Oral Mucosa ◽  
Biosynthetic Pathway ◽  
Fluorescein Isothiocyanate ◽  
Cheek Pouch ◽  
Site Formation ◽  
Induced Responses ◽  
Hamster Cheek Pouch

The purpose of this study was to determine whether methotrexate modulates bradykinin-induced increase in macromolecular efflux from the in situ oral mucosa and whether this response is mediated by thel-arginine/nitric oxide biosynthetic pathway. Using intravital microscopy, we found that suffusion of methotrexate alone onto the hamster cheek pouch had no significant effects on leaky site formation and increase in clearance of fluorescein isothiocyanate-labeled dextran (molecular mass, 70 kDa). However, methotrexate significantly potentiated bradykinin-induced responses ( P < 0.05). These effects were associated with significant increases in nitrites concentration and guanosine 3′,5′-cyclic monophosphate-like immunoreactivity in the suffusate and were abrogated by N G-nitro-l-arginine methyl ester (l-NAME) but not N G-nitro-d-arginine methyl ester (d-NAME).l-Arginine, but notd-arginine, abolishedl-NAME-induced responses. ZnCI2 and indomethacin had no significant effects on methotrexate-induced responses. Methotrexate had no significant effects on adenosine- and ionomycin-induced increases in macromolecular efflux. Collectively, these data indicate that methotrexate amplifies bradykinin-induced increase in macromolecular efflux from the in situ oral mucosa in a specific, receptor- andl-arginine/nitric oxide biosynthetic pathway-dependent fashion.

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