AJP - Regulatory, Integrative and Comparative Physiology, Vol 273, Issue 4 1254-R1262, Copyright © 1997 by American Physiological Society
Methotrexate potentiates bradykinin-induced increase in macromolecular efflux from the hamster oral mucosa
X. P. Gao and I. Rubinstein
Department of Medicine, University of Illinois at Chicago, and the West Side Department of Veterans Affairs Medical Center, 60612-7323, USA.
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 the L-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 not D-arginine, abolished
L-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- and L-arginine/nitric oxide biosynthetic
pathway-dependent fashion.
